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

Gabrielle Romain; Paolo Strati; Ali Rezvan; Mohsen Fathi; Irfan N. Bandey; Jay R.T. Adolacion; Darren S. Heeke; Ivan Liadi; Mario L. Marques-Piubelli; Luisa M. Solis Soto; Ankit Mahendra; Francisco Vega; Laurence J.N. Cooper; Harjeet Singh; Mike Mattie; Adrian Bot; Sattva Neelapu; Navin Varadarajan

doi:10.1172/JCI159402

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: 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: 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 Rezvan, A. in: 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 Fathi, M. in: 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 Bandey, I. in: 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 Adolacion, J. in: 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 Heeke, D. in: 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 Liadi, I. in: 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: 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 Solis Soto, L. in: 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 Mahendra, A. in: 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: 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: 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: 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: 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: 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: 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: PubMed | Google Scholar |

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

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.

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

Article tools

Metrics

Go to

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

Article tools

Metrics

Go to

Sign up for email alerts