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ResearchIn-Press PreviewImmunologyOncology Open Access | 10.1172/JCI174249

Targeted degradation of oncogenic KRASG12V triggers antitumor immunity in lung cancer models

Dezhi Li,1 Ke Geng,1 Yuan Hao,2 Jiajia Gu,3 Saurav Kumar,4 Annabel T. Olson,4 Christina C. Kuismi,4 Hye Mi Kim,3 Yuanwang Pan,1 Fiona Sherman,1 Asia M. Williams,3 Yiting Li,3 Fei Li,5 Ting Chen,1 Cassandra Thakurdin,1 Michela Ranieri,1 Mary Meynardie,1 Daniel S. Levin,1 Janaye Stephens,1 Alison Chafitz,1 Joy Chen,4 Mia S. Donald-Paladino,4 Jaylen M. Powell,1 Ze-Yan Zhang,6 Wei Chen,7 Magdalena Ploszaj,1 Han Han,1 Shengqing Gu,8 Tinghu Zhang,9 Baoli Hu,10 Benjamin A. Nacev,3 Medard Ernest Kaiza,3 Alice H. Berger,4 Xuerui Wang,3 Jing Li,3 Xuejiao Sun,3 Yang Liu,11 Xiaoyang Zhang,12 Tullia C. Bruno,13 Nathanael S. Gray,9 Behnam Nabet,4 Kwok-Kin Wong,1 and Hua Zhang3

1Division of Hematology and Medical Oncology, Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, New York, United States of America

2Applied Bioinformatics Laboratories, Office of Science and Research, New York University Grossman School of Medicine, New York, United States of America

3Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, United States of America

4Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China

6Department of Radiation Oncology, New York University Grossman School of Medicine, New York, United States of America

7Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, United States of America

8Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Chemical and Systems Biology, Chem-H and Stanford Cancer Inst, Stanford University School of Medicine, Stanford, United States of America

10Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

11Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, United States of America

12Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, United States of America

13Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

Find articles by Li, D. in: JCI | PubMed | Google Scholar |

1Division of Hematology and Medical Oncology, Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, New York, United States of America

2Applied Bioinformatics Laboratories, Office of Science and Research, New York University Grossman School of Medicine, New York, United States of America

3Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, United States of America

4Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China

6Department of Radiation Oncology, New York University Grossman School of Medicine, New York, United States of America

7Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, United States of America

8Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Chemical and Systems Biology, Chem-H and Stanford Cancer Inst, Stanford University School of Medicine, Stanford, United States of America

10Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

11Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, United States of America

12Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, United States of America

13Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

Find articles by Geng, K. in: JCI | PubMed | Google Scholar

1Division of Hematology and Medical Oncology, Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, New York, United States of America

2Applied Bioinformatics Laboratories, Office of Science and Research, New York University Grossman School of Medicine, New York, United States of America

3Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, United States of America

4Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China

6Department of Radiation Oncology, New York University Grossman School of Medicine, New York, United States of America

7Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, United States of America

8Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Chemical and Systems Biology, Chem-H and Stanford Cancer Inst, Stanford University School of Medicine, Stanford, United States of America

10Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

11Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, United States of America

12Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, United States of America

13Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

Find articles by Hao, Y. in: JCI | PubMed | Google Scholar

1Division of Hematology and Medical Oncology, Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, New York, United States of America

2Applied Bioinformatics Laboratories, Office of Science and Research, New York University Grossman School of Medicine, New York, United States of America

3Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, United States of America

4Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China

6Department of Radiation Oncology, New York University Grossman School of Medicine, New York, United States of America

7Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, United States of America

8Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Chemical and Systems Biology, Chem-H and Stanford Cancer Inst, Stanford University School of Medicine, Stanford, United States of America

10Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

11Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, United States of America

12Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, United States of America

13Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

Find articles by Gu, J. in: JCI | PubMed | Google Scholar

1Division of Hematology and Medical Oncology, Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, New York, United States of America

2Applied Bioinformatics Laboratories, Office of Science and Research, New York University Grossman School of Medicine, New York, United States of America

3Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, United States of America

4Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China

6Department of Radiation Oncology, New York University Grossman School of Medicine, New York, United States of America

7Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, United States of America

8Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Chemical and Systems Biology, Chem-H and Stanford Cancer Inst, Stanford University School of Medicine, Stanford, United States of America

10Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

11Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, United States of America

12Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, United States of America

13Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

Find articles by Kumar, S. in: JCI | PubMed | Google Scholar

1Division of Hematology and Medical Oncology, Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, New York, United States of America

2Applied Bioinformatics Laboratories, Office of Science and Research, New York University Grossman School of Medicine, New York, United States of America

3Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, United States of America

4Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China

6Department of Radiation Oncology, New York University Grossman School of Medicine, New York, United States of America

7Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, United States of America

8Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Chemical and Systems Biology, Chem-H and Stanford Cancer Inst, Stanford University School of Medicine, Stanford, United States of America

10Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

11Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, United States of America

12Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, United States of America

13Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

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1Division of Hematology and Medical Oncology, Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, New York, United States of America

2Applied Bioinformatics Laboratories, Office of Science and Research, New York University Grossman School of Medicine, New York, United States of America

3Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, United States of America

4Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China

6Department of Radiation Oncology, New York University Grossman School of Medicine, New York, United States of America

7Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, United States of America

8Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Chemical and Systems Biology, Chem-H and Stanford Cancer Inst, Stanford University School of Medicine, Stanford, United States of America

10Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

11Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, United States of America

12Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, United States of America

13Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

Find articles by Kuismi, C. in: JCI | PubMed | Google Scholar

1Division of Hematology and Medical Oncology, Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, New York, United States of America

2Applied Bioinformatics Laboratories, Office of Science and Research, New York University Grossman School of Medicine, New York, United States of America

3Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, United States of America

4Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China

6Department of Radiation Oncology, New York University Grossman School of Medicine, New York, United States of America

7Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, United States of America

8Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Chemical and Systems Biology, Chem-H and Stanford Cancer Inst, Stanford University School of Medicine, Stanford, United States of America

10Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

11Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, United States of America

12Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, United States of America

13Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

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1Division of Hematology and Medical Oncology, Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, New York, United States of America

2Applied Bioinformatics Laboratories, Office of Science and Research, New York University Grossman School of Medicine, New York, United States of America

3Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, United States of America

4Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China

6Department of Radiation Oncology, New York University Grossman School of Medicine, New York, United States of America

7Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, United States of America

8Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Chemical and Systems Biology, Chem-H and Stanford Cancer Inst, Stanford University School of Medicine, Stanford, United States of America

10Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

11Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, United States of America

12Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, United States of America

13Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

Find articles by Pan, Y. in: JCI | PubMed | Google Scholar

1Division of Hematology and Medical Oncology, Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, New York, United States of America

2Applied Bioinformatics Laboratories, Office of Science and Research, New York University Grossman School of Medicine, New York, United States of America

3Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, United States of America

4Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China

6Department of Radiation Oncology, New York University Grossman School of Medicine, New York, United States of America

7Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, United States of America

8Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Chemical and Systems Biology, Chem-H and Stanford Cancer Inst, Stanford University School of Medicine, Stanford, United States of America

10Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

11Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, United States of America

12Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, United States of America

13Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

Find articles by Sherman, F. in: JCI | PubMed | Google Scholar |

1Division of Hematology and Medical Oncology, Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, New York, United States of America

2Applied Bioinformatics Laboratories, Office of Science and Research, New York University Grossman School of Medicine, New York, United States of America

3Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, United States of America

4Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China

6Department of Radiation Oncology, New York University Grossman School of Medicine, New York, United States of America

7Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, United States of America

8Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Chemical and Systems Biology, Chem-H and Stanford Cancer Inst, Stanford University School of Medicine, Stanford, United States of America

10Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

11Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, United States of America

12Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, United States of America

13Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

Find articles by Williams, A. in: JCI | PubMed | Google Scholar

1Division of Hematology and Medical Oncology, Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, New York, United States of America

2Applied Bioinformatics Laboratories, Office of Science and Research, New York University Grossman School of Medicine, New York, United States of America

3Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, United States of America

4Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China

6Department of Radiation Oncology, New York University Grossman School of Medicine, New York, United States of America

7Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, United States of America

8Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Chemical and Systems Biology, Chem-H and Stanford Cancer Inst, Stanford University School of Medicine, Stanford, United States of America

10Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

11Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, United States of America

12Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, United States of America

13Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

Find articles by Li, Y. in: JCI | PubMed | Google Scholar

1Division of Hematology and Medical Oncology, Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, New York, United States of America

2Applied Bioinformatics Laboratories, Office of Science and Research, New York University Grossman School of Medicine, New York, United States of America

3Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, United States of America

4Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China

6Department of Radiation Oncology, New York University Grossman School of Medicine, New York, United States of America

7Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, United States of America

8Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Chemical and Systems Biology, Chem-H and Stanford Cancer Inst, Stanford University School of Medicine, Stanford, United States of America

10Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

11Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, United States of America

12Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, United States of America

13Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

Find articles by Li, F. in: JCI | PubMed | Google Scholar

1Division of Hematology and Medical Oncology, Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, New York, United States of America

2Applied Bioinformatics Laboratories, Office of Science and Research, New York University Grossman School of Medicine, New York, United States of America

3Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, United States of America

4Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China

6Department of Radiation Oncology, New York University Grossman School of Medicine, New York, United States of America

7Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, United States of America

8Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Chemical and Systems Biology, Chem-H and Stanford Cancer Inst, Stanford University School of Medicine, Stanford, United States of America

10Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

11Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, United States of America

12Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, United States of America

13Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

Find articles by Chen, T. in: JCI | PubMed | Google Scholar

1Division of Hematology and Medical Oncology, Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, New York, United States of America

2Applied Bioinformatics Laboratories, Office of Science and Research, New York University Grossman School of Medicine, New York, United States of America

3Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, United States of America

4Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China

6Department of Radiation Oncology, New York University Grossman School of Medicine, New York, United States of America

7Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, United States of America

8Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Chemical and Systems Biology, Chem-H and Stanford Cancer Inst, Stanford University School of Medicine, Stanford, United States of America

10Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

11Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, United States of America

12Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, United States of America

13Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

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1Division of Hematology and Medical Oncology, Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, New York, United States of America

2Applied Bioinformatics Laboratories, Office of Science and Research, New York University Grossman School of Medicine, New York, United States of America

3Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, United States of America

4Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China

6Department of Radiation Oncology, New York University Grossman School of Medicine, New York, United States of America

7Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, United States of America

8Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Chemical and Systems Biology, Chem-H and Stanford Cancer Inst, Stanford University School of Medicine, Stanford, United States of America

10Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

11Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, United States of America

12Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, United States of America

13Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

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1Division of Hematology and Medical Oncology, Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, New York, United States of America

2Applied Bioinformatics Laboratories, Office of Science and Research, New York University Grossman School of Medicine, New York, United States of America

3Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, United States of America

4Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China

6Department of Radiation Oncology, New York University Grossman School of Medicine, New York, United States of America

7Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, United States of America

8Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Chemical and Systems Biology, Chem-H and Stanford Cancer Inst, Stanford University School of Medicine, Stanford, United States of America

10Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

11Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, United States of America

12Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, United States of America

13Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

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1Division of Hematology and Medical Oncology, Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, New York, United States of America

2Applied Bioinformatics Laboratories, Office of Science and Research, New York University Grossman School of Medicine, New York, United States of America

3Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, United States of America

4Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China

6Department of Radiation Oncology, New York University Grossman School of Medicine, New York, United States of America

7Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, United States of America

8Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Chemical and Systems Biology, Chem-H and Stanford Cancer Inst, Stanford University School of Medicine, Stanford, United States of America

10Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

11Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, United States of America

12Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, United States of America

13Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

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1Division of Hematology and Medical Oncology, Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, New York, United States of America

2Applied Bioinformatics Laboratories, Office of Science and Research, New York University Grossman School of Medicine, New York, United States of America

3Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, United States of America

4Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China

6Department of Radiation Oncology, New York University Grossman School of Medicine, New York, United States of America

7Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, United States of America

8Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Chemical and Systems Biology, Chem-H and Stanford Cancer Inst, Stanford University School of Medicine, Stanford, United States of America

10Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

11Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, United States of America

12Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, United States of America

13Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

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1Division of Hematology and Medical Oncology, Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, New York, United States of America

2Applied Bioinformatics Laboratories, Office of Science and Research, New York University Grossman School of Medicine, New York, United States of America

3Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, United States of America

4Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China

6Department of Radiation Oncology, New York University Grossman School of Medicine, New York, United States of America

7Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, United States of America

8Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Chemical and Systems Biology, Chem-H and Stanford Cancer Inst, Stanford University School of Medicine, Stanford, United States of America

10Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

11Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, United States of America

12Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, United States of America

13Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

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1Division of Hematology and Medical Oncology, Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, New York, United States of America

2Applied Bioinformatics Laboratories, Office of Science and Research, New York University Grossman School of Medicine, New York, United States of America

3Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, United States of America

4Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China

6Department of Radiation Oncology, New York University Grossman School of Medicine, New York, United States of America

7Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, United States of America

8Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Chemical and Systems Biology, Chem-H and Stanford Cancer Inst, Stanford University School of Medicine, Stanford, United States of America

10Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

11Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, United States of America

12Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, United States of America

13Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

Find articles by Chen, J. in: JCI | PubMed | Google Scholar

1Division of Hematology and Medical Oncology, Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, New York, United States of America

2Applied Bioinformatics Laboratories, Office of Science and Research, New York University Grossman School of Medicine, New York, United States of America

3Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, United States of America

4Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China

6Department of Radiation Oncology, New York University Grossman School of Medicine, New York, United States of America

7Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, United States of America

8Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Chemical and Systems Biology, Chem-H and Stanford Cancer Inst, Stanford University School of Medicine, Stanford, United States of America

10Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

11Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, United States of America

12Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, United States of America

13Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

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3Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, United States of America

4Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China

6Department of Radiation Oncology, New York University Grossman School of Medicine, New York, United States of America

7Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, United States of America

8Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Chemical and Systems Biology, Chem-H and Stanford Cancer Inst, Stanford University School of Medicine, Stanford, United States of America

10Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

11Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, United States of America

12Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, United States of America

13Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

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2Applied Bioinformatics Laboratories, Office of Science and Research, New York University Grossman School of Medicine, New York, United States of America

3Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, United States of America

4Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China

6Department of Radiation Oncology, New York University Grossman School of Medicine, New York, United States of America

7Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, United States of America

8Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Chemical and Systems Biology, Chem-H and Stanford Cancer Inst, Stanford University School of Medicine, Stanford, United States of America

10Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

11Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, United States of America

12Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, United States of America

13Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

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2Applied Bioinformatics Laboratories, Office of Science and Research, New York University Grossman School of Medicine, New York, United States of America

3Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, United States of America

4Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China

6Department of Radiation Oncology, New York University Grossman School of Medicine, New York, United States of America

7Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, United States of America

8Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Chemical and Systems Biology, Chem-H and Stanford Cancer Inst, Stanford University School of Medicine, Stanford, United States of America

10Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

11Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, United States of America

12Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, United States of America

13Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

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2Applied Bioinformatics Laboratories, Office of Science and Research, New York University Grossman School of Medicine, New York, United States of America

3Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, United States of America

4Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China

6Department of Radiation Oncology, New York University Grossman School of Medicine, New York, United States of America

7Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, United States of America

8Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Chemical and Systems Biology, Chem-H and Stanford Cancer Inst, Stanford University School of Medicine, Stanford, United States of America

10Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

11Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, United States of America

12Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, United States of America

13Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

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3Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, United States of America

4Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China

6Department of Radiation Oncology, New York University Grossman School of Medicine, New York, United States of America

7Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, United States of America

8Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Chemical and Systems Biology, Chem-H and Stanford Cancer Inst, Stanford University School of Medicine, Stanford, United States of America

10Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

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3Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, United States of America

4Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China

6Department of Radiation Oncology, New York University Grossman School of Medicine, New York, United States of America

7Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, United States of America

8Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Chemical and Systems Biology, Chem-H and Stanford Cancer Inst, Stanford University School of Medicine, Stanford, United States of America

10Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

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13Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

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3Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, United States of America

4Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China

6Department of Radiation Oncology, New York University Grossman School of Medicine, New York, United States of America

7Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, United States of America

8Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Chemical and Systems Biology, Chem-H and Stanford Cancer Inst, Stanford University School of Medicine, Stanford, United States of America

10Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

11Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, United States of America

12Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, United States of America

13Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

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3Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, United States of America

4Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China

6Department of Radiation Oncology, New York University Grossman School of Medicine, New York, United States of America

7Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, United States of America

8Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Chemical and Systems Biology, Chem-H and Stanford Cancer Inst, Stanford University School of Medicine, Stanford, United States of America

10Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

11Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, United States of America

12Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, United States of America

13Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

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3Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, United States of America

4Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China

6Department of Radiation Oncology, New York University Grossman School of Medicine, New York, United States of America

7Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, United States of America

8Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Chemical and Systems Biology, Chem-H and Stanford Cancer Inst, Stanford University School of Medicine, Stanford, United States of America

10Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

11Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, United States of America

12Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, United States of America

13Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

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3Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, United States of America

4Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China

6Department of Radiation Oncology, New York University Grossman School of Medicine, New York, United States of America

7Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, United States of America

8Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Chemical and Systems Biology, Chem-H and Stanford Cancer Inst, Stanford University School of Medicine, Stanford, United States of America

10Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

11Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, United States of America

12Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, United States of America

13Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

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3Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, United States of America

4Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China

6Department of Radiation Oncology, New York University Grossman School of Medicine, New York, United States of America

7Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, United States of America

8Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Chemical and Systems Biology, Chem-H and Stanford Cancer Inst, Stanford University School of Medicine, Stanford, United States of America

10Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

11Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, United States of America

12Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, United States of America

13Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

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3Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, United States of America

4Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China

6Department of Radiation Oncology, New York University Grossman School of Medicine, New York, United States of America

7Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, United States of America

8Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Chemical and Systems Biology, Chem-H and Stanford Cancer Inst, Stanford University School of Medicine, Stanford, United States of America

10Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

11Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, United States of America

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13Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

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5Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China

6Department of Radiation Oncology, New York University Grossman School of Medicine, New York, United States of America

7Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, United States of America

8Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Chemical and Systems Biology, Chem-H and Stanford Cancer Inst, Stanford University School of Medicine, Stanford, United States of America

10Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

11Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, United States of America

12Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, United States of America

13Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

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3Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, United States of America

4Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China

6Department of Radiation Oncology, New York University Grossman School of Medicine, New York, United States of America

7Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, United States of America

8Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Chemical and Systems Biology, Chem-H and Stanford Cancer Inst, Stanford University School of Medicine, Stanford, United States of America

10Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

11Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, United States of America

12Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, United States of America

13Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

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3Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, United States of America

4Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China

6Department of Radiation Oncology, New York University Grossman School of Medicine, New York, United States of America

7Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, United States of America

8Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Chemical and Systems Biology, Chem-H and Stanford Cancer Inst, Stanford University School of Medicine, Stanford, United States of America

10Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

11Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, United States of America

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5Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China

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7Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, United States of America

8Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Chemical and Systems Biology, Chem-H and Stanford Cancer Inst, Stanford University School of Medicine, Stanford, United States of America

10Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

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5Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China

6Department of Radiation Oncology, New York University Grossman School of Medicine, New York, United States of America

7Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, United States of America

8Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Chemical and Systems Biology, Chem-H and Stanford Cancer Inst, Stanford University School of Medicine, Stanford, United States of America

10Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

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3Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, United States of America

4Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China

6Department of Radiation Oncology, New York University Grossman School of Medicine, New York, United States of America

7Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, United States of America

8Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Chemical and Systems Biology, Chem-H and Stanford Cancer Inst, Stanford University School of Medicine, Stanford, United States of America

10Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

11Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, United States of America

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3Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, United States of America

4Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China

6Department of Radiation Oncology, New York University Grossman School of Medicine, New York, United States of America

7Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, United States of America

8Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Chemical and Systems Biology, Chem-H and Stanford Cancer Inst, Stanford University School of Medicine, Stanford, United States of America

10Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

11Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, United States of America

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13Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

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4Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China

6Department of Radiation Oncology, New York University Grossman School of Medicine, New York, United States of America

7Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, United States of America

8Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Chemical and Systems Biology, Chem-H and Stanford Cancer Inst, Stanford University School of Medicine, Stanford, United States of America

10Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

11Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, United States of America

12Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, United States of America

13Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

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3Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, United States of America

4Human Biology Division, Fred Hutchinson Cancer Center, Seattle, United States of America

5Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China

6Department of Radiation Oncology, New York University Grossman School of Medicine, New York, United States of America

7Division of Pulmonary Medicine, Department of Pediatrics, UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh, Pittsburgh, United States of America

8Department of Hematopoietic Biology and Malignancy, University of Texas MD Anderson Cancer Center, Houston, United States of America

9Department of Chemical and Systems Biology, Chem-H and Stanford Cancer Inst, Stanford University School of Medicine, Stanford, United States of America

10Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

11Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, United States of America

12Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, United States of America

13Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, United States of America

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Published December 24, 2024 - More info

J Clin Invest. https://doi.org/10.1172/JCI174249.
Copyright © 2024, Li et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published December 24, 2024 - Version history
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Abstract

KRAS is the most frequently mutated oncogene in lung adenocarcinoma, with G12C and G12V being the most predominant forms. Recent breakthroughs in KRASG12C inhibitors have transformed the clinical management of patients with G12C mutation and advanced our understanding of its function. However, little is known about the targeted disruption of KRASG12V, partly due to a lack of specific inhibitors. Here, we leverage the degradation tag (dTAG) system to develop a KRASG12V transgenic mouse model. We explore the therapeutic potential of KRASG12V degradation and characterize its impact on the tumor microenvironment (TME). Our study reveals that degrading KRASG12V abolishes lung and pancreatic tumors in mice and causes a robust inhibition of KRAS-regulated cancer intrinsic signaling. Importantly, targeted degradation of KRASG12V reprograms the TME towards a stimulatory milieu and drives antitumor immunity, elicited mainly by effector and cytotoxic CD8+ T cells. Our work provides important insights into the impact of degrading KRASG12V on both tumor progression and immune response, highlighting degraders as a powerful strategy for targeting KRAS mutant cancers.

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