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ResearchIn-Press PreviewOncology Open Access | 10.1172/JCI180282
1Department of Urology, Stanford University School of Medicine, Stanford, United States of America
2Department of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, United States of America
3Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, United States of America
4Department of Medicine, UCSF, San Francisco, United States of America
5Department of Radiology, Stanford University School of Medicine, Stanford, United States of America
6Department of Pathology, Stanford University School of Medicine, Stanford, United States of America
7Department of Biological Engineering, Department of Chemical Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, United States of America
Find articles by Wen, R. in: JCI | PubMed | Google Scholar
1Department of Urology, Stanford University School of Medicine, Stanford, United States of America
2Department of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, United States of America
3Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, United States of America
4Department of Medicine, UCSF, San Francisco, United States of America
5Department of Radiology, Stanford University School of Medicine, Stanford, United States of America
6Department of Pathology, Stanford University School of Medicine, Stanford, United States of America
7Department of Biological Engineering, Department of Chemical Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, United States of America
Find articles by Stark, J. in: JCI | PubMed | Google Scholar
1Department of Urology, Stanford University School of Medicine, Stanford, United States of America
2Department of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, United States of America
3Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, United States of America
4Department of Medicine, UCSF, San Francisco, United States of America
5Department of Radiology, Stanford University School of Medicine, Stanford, United States of America
6Department of Pathology, Stanford University School of Medicine, Stanford, United States of America
7Department of Biological Engineering, Department of Chemical Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, United States of America
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1Department of Urology, Stanford University School of Medicine, Stanford, United States of America
2Department of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, United States of America
3Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, United States of America
4Department of Medicine, UCSF, San Francisco, United States of America
5Department of Radiology, Stanford University School of Medicine, Stanford, United States of America
6Department of Pathology, Stanford University School of Medicine, Stanford, United States of America
7Department of Biological Engineering, Department of Chemical Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, United States of America
Find articles by Fan, Z. in: JCI | PubMed | Google Scholar
1Department of Urology, Stanford University School of Medicine, Stanford, United States of America
2Department of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, United States of America
3Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, United States of America
4Department of Medicine, UCSF, San Francisco, United States of America
5Department of Radiology, Stanford University School of Medicine, Stanford, United States of America
6Department of Pathology, Stanford University School of Medicine, Stanford, United States of America
7Department of Biological Engineering, Department of Chemical Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, United States of America
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1Department of Urology, Stanford University School of Medicine, Stanford, United States of America
2Department of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, United States of America
3Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, United States of America
4Department of Medicine, UCSF, San Francisco, United States of America
5Department of Radiology, Stanford University School of Medicine, Stanford, United States of America
6Department of Pathology, Stanford University School of Medicine, Stanford, United States of America
7Department of Biological Engineering, Department of Chemical Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, United States of America
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1Department of Urology, Stanford University School of Medicine, Stanford, United States of America
2Department of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, United States of America
3Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, United States of America
4Department of Medicine, UCSF, San Francisco, United States of America
5Department of Radiology, Stanford University School of Medicine, Stanford, United States of America
6Department of Pathology, Stanford University School of Medicine, Stanford, United States of America
7Department of Biological Engineering, Department of Chemical Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, United States of America
Find articles by Zhang, X. in: JCI | PubMed | Google Scholar
1Department of Urology, Stanford University School of Medicine, Stanford, United States of America
2Department of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, United States of America
3Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, United States of America
4Department of Medicine, UCSF, San Francisco, United States of America
5Department of Radiology, Stanford University School of Medicine, Stanford, United States of America
6Department of Pathology, Stanford University School of Medicine, Stanford, United States of America
7Department of Biological Engineering, Department of Chemical Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, United States of America
Find articles by Riley, N. in: JCI | PubMed | Google Scholar |
1Department of Urology, Stanford University School of Medicine, Stanford, United States of America
2Department of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, United States of America
3Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, United States of America
4Department of Medicine, UCSF, San Francisco, United States of America
5Department of Radiology, Stanford University School of Medicine, Stanford, United States of America
6Department of Pathology, Stanford University School of Medicine, Stanford, United States of America
7Department of Biological Engineering, Department of Chemical Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, United States of America
Find articles by Totten, S. in: JCI | PubMed | Google Scholar
1Department of Urology, Stanford University School of Medicine, Stanford, United States of America
2Department of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, United States of America
3Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, United States of America
4Department of Medicine, UCSF, San Francisco, United States of America
5Department of Radiology, Stanford University School of Medicine, Stanford, United States of America
6Department of Pathology, Stanford University School of Medicine, Stanford, United States of America
7Department of Biological Engineering, Department of Chemical Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, United States of America
Find articles by Bermudez, A. in: JCI | PubMed | Google Scholar
1Department of Urology, Stanford University School of Medicine, Stanford, United States of America
2Department of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, United States of America
3Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, United States of America
4Department of Medicine, UCSF, San Francisco, United States of America
5Department of Radiology, Stanford University School of Medicine, Stanford, United States of America
6Department of Pathology, Stanford University School of Medicine, Stanford, United States of America
7Department of Biological Engineering, Department of Chemical Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, United States of America
Find articles by Nolley, R. in: JCI | PubMed | Google Scholar
1Department of Urology, Stanford University School of Medicine, Stanford, United States of America
2Department of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, United States of America
3Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, United States of America
4Department of Medicine, UCSF, San Francisco, United States of America
5Department of Radiology, Stanford University School of Medicine, Stanford, United States of America
6Department of Pathology, Stanford University School of Medicine, Stanford, United States of America
7Department of Biological Engineering, Department of Chemical Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, United States of America
Find articles by Zhao, H. in: JCI | PubMed | Google Scholar
1Department of Urology, Stanford University School of Medicine, Stanford, United States of America
2Department of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, United States of America
3Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, United States of America
4Department of Medicine, UCSF, San Francisco, United States of America
5Department of Radiology, Stanford University School of Medicine, Stanford, United States of America
6Department of Pathology, Stanford University School of Medicine, Stanford, United States of America
7Department of Biological Engineering, Department of Chemical Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, United States of America
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1Department of Urology, Stanford University School of Medicine, Stanford, United States of America
2Department of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, United States of America
3Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, United States of America
4Department of Medicine, UCSF, San Francisco, United States of America
5Department of Radiology, Stanford University School of Medicine, Stanford, United States of America
6Department of Pathology, Stanford University School of Medicine, Stanford, United States of America
7Department of Biological Engineering, Department of Chemical Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, United States of America
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1Department of Urology, Stanford University School of Medicine, Stanford, United States of America
2Department of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, United States of America
3Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, United States of America
4Department of Medicine, UCSF, San Francisco, United States of America
5Department of Radiology, Stanford University School of Medicine, Stanford, United States of America
6Department of Pathology, Stanford University School of Medicine, Stanford, United States of America
7Department of Biological Engineering, Department of Chemical Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, United States of America
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1Department of Urology, Stanford University School of Medicine, Stanford, United States of America
2Department of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, United States of America
3Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, United States of America
4Department of Medicine, UCSF, San Francisco, United States of America
5Department of Radiology, Stanford University School of Medicine, Stanford, United States of America
6Department of Pathology, Stanford University School of Medicine, Stanford, United States of America
7Department of Biological Engineering, Department of Chemical Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, United States of America
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1Department of Urology, Stanford University School of Medicine, Stanford, United States of America
2Department of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, United States of America
3Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, United States of America
4Department of Medicine, UCSF, San Francisco, United States of America
5Department of Radiology, Stanford University School of Medicine, Stanford, United States of America
6Department of Pathology, Stanford University School of Medicine, Stanford, United States of America
7Department of Biological Engineering, Department of Chemical Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, United States of America
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Published October 22, 2024 - More info
Prostate cancer is the second leading cause of male cancer death in the U.S. Current immune checkpoint inhibitor-based immunotherapies have improved survival for many malignancies; however, they have failed to prolong survival for prostate cancer. Siglecs (sialic acid-binding immunoglobulin-like lectins) are expressed on immune cells and regulate immune responses and function. Siglec-7 and Siglec-9 contribute to immune evasion by interacting with their ligands. However, the role of Siglec-7/9 receptors and their ligands in prostate cancer remains poorly understood. Here, we find that Siglec-7 and Siglec-9 are associated with poor prognosis in prostate cancer patients, and are highly expressed in myeloid cells, including macrophages, in prostate tumor tissues. Siglecs-7 and -9 ligands were expressed in prostate cancer cells and human prostate tumor tissues. Blocking the interactions between Siglec-7/9 and sialic acids inhibited prostate cancer xenograft growth and increased immune cell infiltration in humanized mice in vivo. Using a CRISPRi screen and mass spectrometry, we identified CD59 as a candidate Siglec-9 ligand in prostate cancer. The identification of Siglecs-7 and -9 as potential therapeutic targets, including CD59/Siglec-9 axis, opens up opportunities for immune-based interventions in prostate cancer.