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ResearchIn-Press PreviewImmunologyOncology Open Access | 10.1172/JCI159402

Multidimensional single-cell analysis identifies a role for CD2-CD58 interactions in clinical antitumor T cell responses

Gabrielle Romain,1 Paolo Strati,2 Ali Rezvan,1 Mohsen Fathi,3 Irfan N. Bandey,1 Jay R.T. Adolacion,1 Darren S. Heeke,4 Ivan Liadi,1 Mario L. Marques-Piubelli,5 Luisa M. Solis Soto,5 Ankit Mahendra,1 Francisco Vega,5 Laurence J.N. Cooper,3 Harjeet Singh,6 Mike Mattie,7 Adrian Bot,8 Sattva Neelapu,2 and Navin Varadarajan1

1Department of Chemical and Biomolecular Engineering, University of Houston, Houston, United States of America

2Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, United States of America

3CellChorus, Houston, United States of America

4Kite, Gilead company, Santa Monica, United States of America

5Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, United States of America

6Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, United States of America

7Kite, a Gilead company, Santa Monica, United States of America

8Chief Scientific Officer, Kite, a Gilead company, Santa Monica, United States of America

Find articles by Romain, G. in: JCI | PubMed | Google Scholar

1Department of Chemical and Biomolecular Engineering, University of Houston, Houston, United States of America

2Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, United States of America

3CellChorus, Houston, United States of America

4Kite, Gilead company, Santa Monica, United States of America

5Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, United States of America

6Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, United States of America

7Kite, a Gilead company, Santa Monica, United States of America

8Chief Scientific Officer, Kite, a Gilead company, Santa Monica, United States of America

Find articles by Strati, P. in: JCI | PubMed | Google Scholar

1Department of Chemical and Biomolecular Engineering, University of Houston, Houston, United States of America

2Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, United States of America

3CellChorus, Houston, United States of America

4Kite, Gilead company, Santa Monica, United States of America

5Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, United States of America

6Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, United States of America

7Kite, a Gilead company, Santa Monica, United States of America

8Chief Scientific Officer, Kite, a Gilead company, Santa Monica, United States of America

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1Department of Chemical and Biomolecular Engineering, University of Houston, Houston, United States of America

2Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, United States of America

3CellChorus, Houston, United States of America

4Kite, Gilead company, Santa Monica, United States of America

5Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, United States of America

6Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, United States of America

7Kite, a Gilead company, Santa Monica, United States of America

8Chief Scientific Officer, Kite, a Gilead company, Santa Monica, United States of America

Find articles by Fathi, M. in: JCI | PubMed | Google Scholar |

1Department of Chemical and Biomolecular Engineering, University of Houston, Houston, United States of America

2Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, United States of America

3CellChorus, Houston, United States of America

4Kite, Gilead company, Santa Monica, United States of America

5Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, United States of America

6Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, United States of America

7Kite, a Gilead company, Santa Monica, United States of America

8Chief Scientific Officer, Kite, a Gilead company, Santa Monica, United States of America

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1Department of Chemical and Biomolecular Engineering, University of Houston, Houston, United States of America

2Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, United States of America

3CellChorus, Houston, United States of America

4Kite, Gilead company, Santa Monica, United States of America

5Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, United States of America

6Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, United States of America

7Kite, a Gilead company, Santa Monica, United States of America

8Chief Scientific Officer, Kite, a Gilead company, Santa Monica, United States of America

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1Department of Chemical and Biomolecular Engineering, University of Houston, Houston, United States of America

2Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, United States of America

3CellChorus, Houston, United States of America

4Kite, Gilead company, Santa Monica, United States of America

5Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, United States of America

6Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, United States of America

7Kite, a Gilead company, Santa Monica, United States of America

8Chief Scientific Officer, Kite, a Gilead company, Santa Monica, United States of America

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1Department of Chemical and Biomolecular Engineering, University of Houston, Houston, United States of America

2Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, United States of America

3CellChorus, Houston, United States of America

4Kite, Gilead company, Santa Monica, United States of America

5Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, United States of America

6Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, United States of America

7Kite, a Gilead company, Santa Monica, United States of America

8Chief Scientific Officer, Kite, a Gilead company, Santa Monica, United States of America

Find articles by Liadi, I. in: JCI | PubMed | Google Scholar

1Department of Chemical and Biomolecular Engineering, University of Houston, Houston, United States of America

2Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, United States of America

3CellChorus, Houston, United States of America

4Kite, Gilead company, Santa Monica, United States of America

5Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, United States of America

6Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, United States of America

7Kite, a Gilead company, Santa Monica, United States of America

8Chief Scientific Officer, Kite, a Gilead company, Santa Monica, United States of America

Find articles by Marques-Piubelli, M. in: JCI | PubMed | Google Scholar |

1Department of Chemical and Biomolecular Engineering, University of Houston, Houston, United States of America

2Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, United States of America

3CellChorus, Houston, United States of America

4Kite, Gilead company, Santa Monica, United States of America

5Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, United States of America

6Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, United States of America

7Kite, a Gilead company, Santa Monica, United States of America

8Chief Scientific Officer, Kite, a Gilead company, Santa Monica, United States of America

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1Department of Chemical and Biomolecular Engineering, University of Houston, Houston, United States of America

2Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, United States of America

3CellChorus, Houston, United States of America

4Kite, Gilead company, Santa Monica, United States of America

5Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, United States of America

6Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, United States of America

7Kite, a Gilead company, Santa Monica, United States of America

8Chief Scientific Officer, Kite, a Gilead company, Santa Monica, United States of America

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

1Department of Chemical and Biomolecular Engineering, University of Houston, Houston, United States of America

2Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, United States of America

3CellChorus, Houston, United States of America

4Kite, Gilead company, Santa Monica, United States of America

5Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, United States of America

6Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, United States of America

7Kite, a Gilead company, Santa Monica, United States of America

8Chief Scientific Officer, Kite, a Gilead company, Santa Monica, United States of America

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

1Department of Chemical and Biomolecular Engineering, University of Houston, Houston, United States of America

2Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, United States of America

3CellChorus, Houston, United States of America

4Kite, Gilead company, Santa Monica, United States of America

5Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, United States of America

6Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, United States of America

7Kite, a Gilead company, Santa Monica, United States of America

8Chief Scientific Officer, Kite, a Gilead company, Santa Monica, United States of America

Find articles by Cooper, L. in: JCI | PubMed | Google Scholar

1Department of Chemical and Biomolecular Engineering, University of Houston, Houston, United States of America

2Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, United States of America

3CellChorus, Houston, United States of America

4Kite, Gilead company, Santa Monica, United States of America

5Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, United States of America

6Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, United States of America

7Kite, a Gilead company, Santa Monica, United States of America

8Chief Scientific Officer, Kite, a Gilead company, Santa Monica, United States of America

Find articles by Singh, H. in: JCI | PubMed | Google Scholar |

1Department of Chemical and Biomolecular Engineering, University of Houston, Houston, United States of America

2Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, United States of America

3CellChorus, Houston, United States of America

4Kite, Gilead company, Santa Monica, United States of America

5Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, United States of America

6Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, United States of America

7Kite, a Gilead company, Santa Monica, United States of America

8Chief Scientific Officer, Kite, a Gilead company, Santa Monica, United States of America

Find articles by Mattie, M. in: JCI | PubMed | Google Scholar

1Department of Chemical and Biomolecular Engineering, University of Houston, Houston, United States of America

2Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, United States of America

3CellChorus, Houston, United States of America

4Kite, Gilead company, Santa Monica, United States of America

5Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, United States of America

6Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, United States of America

7Kite, a Gilead company, Santa Monica, United States of America

8Chief Scientific Officer, Kite, a Gilead company, Santa Monica, United States of America

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

1Department of Chemical and Biomolecular Engineering, University of Houston, Houston, United States of America

2Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, United States of America

3CellChorus, Houston, United States of America

4Kite, Gilead company, Santa Monica, United States of America

5Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, United States of America

6Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, United States of America

7Kite, a Gilead company, Santa Monica, United States of America

8Chief Scientific Officer, Kite, a Gilead company, Santa Monica, United States of America

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

1Department of Chemical and Biomolecular Engineering, University of Houston, Houston, United States of America

2Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, United States of America

3CellChorus, Houston, United States of America

4Kite, Gilead company, Santa Monica, United States of America

5Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, United States of America

6Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, United States of America

7Kite, a Gilead company, Santa Monica, United States of America

8Chief Scientific Officer, Kite, a Gilead company, Santa Monica, United States of America

Find articles by Varadarajan, N. in: JCI | PubMed | Google Scholar |

Published July 26, 2022 - More info

J Clin Invest. https://doi.org/10.1172/JCI159402.
Copyright © 2022, Romain 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 July 26, 2022 - Version history
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Abstract

The in vivo persistence of adoptively transferred T cells is predictive of anti-tumor response. Identifying functional properties of infused T cells that lead to in vivo persistence and tumor eradication has remained elusive. We profiled CD19-specific CAR T cells that comprise the infusion products used to treat large B cell lymphomas using high-throughput single-cell technologies based on Timelapse Imaging Microscopy In Nanowell Grids (TIMING) that integrates killing, cytokine secretion, and transcriptional profiling. Our results show that the directional migration of CD19-specific CAR T cells is correlated with multifunctionality. We identified that CD2 on T cells is associated with directional migration and that the interaction between CD2 on T cells and CD58 on lymphoma cells accelerates killing and serial killing. Consistent with this, we observed elevated CD58 expression on pre-treatment tumor samples in patients with relapsed or refractory large B cell lymphomas treated with CD19-specific CAR T cell therapy was associated with complete clinical response and survival. These results highlight the importance of studying dynamic T-cell tumor cell interactions in identifying optimal antitumor responses.

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Version history
  • Version 1 (July 26, 2022): In-Press Preview
  • Version 2 (September 1, 2022): Electronic publication
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