@article{e2bf9e39d3144b7aa8f7b7930026abff,
title = "Multidimensional single-cell analysis identifies a role for CD2-CD58 interactions in clinical antitumor T cell responses",
abstract = "The in vivo persistence of adoptively transferred T cells is predictive of antitumor response. Identifying functional properties of infused T cells that lead to in vivo persistence and tumor eradication has remained elusive. We profiled CD19-specific chimeric antigen receptor (CAR) T cells as the infusion products used to treat large B cell lymphomas using high-throughput single-cell technologies based on time-lapse imaging microscopy in nanowell grids (TIMING), which 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 showed 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 that elevated CD58 expression on pretreatment 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.",
keywords = "Cancer immunotherapy, Immunology, Oncology",
author = "Gabrielle Romain and Paolo Strati and Ali Rezvan and Mohsen Fathi and Bandey, {Irfan N.} and Adolacion, {Jay R.T.} and Darren Heeke and Ivan Liadi and Marques-Piubelli, {Mario L.} and Solis, {Luisa M.} and Ankit Mahendra and Francisco Vega and Cooper, {Laurence J.N.} and Harjeet Singh and Mike Mattie and Adrian Bot and Neelapu, {Sattva S.} and Navin Varadarajan",
note = "Funding Information: This publication was supported by the NIH (R01GM143243, P30 CA016672); the Cancer Prevention & Research Institute of Texas (CPRIT) (RP180466); a Melanoma Research Alliance (MRA) Established Investigator Award to NV (509800), the National Science Foundation (NSF) (1705464); Congressionally Directed Medical Research Programs (CDMRP) (CA160591); the Owens Foundation (to NV); The University of Texas MD Anderson Cancer Center B-Cell Lymphoma Moonshot (to SSN); CRISPR Therapeutics; and the Geron Corp. (FV). We would like to acknowledge the MD Anderson Cancer Center Flow Cytometry and Cellular Imaging Core Facility for FACS sorting (NCI P30CA16672), the University of Houston Seq-N-Edit Core for RNA-Seq, Intel for the loan of the computing cluster, and the University of Houston Center for Advanced Computing and Data Systems (CACDS) for high-performance computing facilities. We thank Riccardo Dal-la-Favera for sharing the HBL-1 cell lines. Funding Information: This publication was supported by the NIH (R01GM143243, P30 CA016672); the Cancer Prevention & Research Institute of Texas (CPRIT) (RP180466); a Melanoma Research Alliance (MRA) Established Investigator Award to NV (509800), the National Science Foundation (NSF) (1705464); Congressionally Directed Medical Research Programs (CDMRP) (CA160591); the Owens Foundation (to NV); The University of Texas MD Anderson Cancer Center B-Cell Lymphoma Moonshot (to SSN); CRISPR Therapeutics; and the Geron Corp. (FV). We would like to acknowledge the MD Anderson Cancer Center Flow Cytometry and Cellular Imaging Core Facility for FACS sorting (NCI P30CA16672), the University of Houston Seq-N-Edit Core for RNA-Seq, Intel for the loan of the computing cluster, and the University of Houston Center for Advanced Computing and Data Systems (CACDS) for high-performance computing facilities. We thank Riccardo Dalla-Favera for sharing the HBL-1 cell lines. Publisher Copyright: {\textcopyright} 2022 American Society for Clinical Investigation. All rights reserved.",
year = "2022",
month = sep,
day = "1",
doi = "10.1172/JCI159402",
language = "English (US)",
volume = "132",
journal = "The Journal of clinical investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "17",
}