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

• Published in: The Journal of clinical investigation Vol. 132; no. 17; pp. 1 - 10
• Main Authors: Romain, Gabrielle, Strati, Paolo, Rezvan, Ali, Fathi, Mohsen, Bandey, Irfan N., Adolacion, Jay R T., Heeke, Darren, Liadi, Ivan, Marques-Piubelli, Mario L., Solis, Luisa M., Mahendra, Ankit, Vega, Francisco, Cooper, Laurence J.N., Singh, Harjeet, Mattie, Mike, Bot, Adrian, Neelapu, Sattva S., Varadarajan, Navin
• Format: Journal Article
• Language: English
• Published: Ann Arbor American Society for Clinical Investigation 01.09.2022
• Subjects: Antigens; Antitumor activity; Apoptosis; B-cell lymphoma; Biomedical research; Cancer; Care and treatment; CD19 antigen; CD58 antigen; Cell adhesion molecules; Cell interactions; Cell therapy; Chimeric antigen receptors; Cytokines; Development and progression; Drug therapy; Health aspects; Immune response; Immunology; Lymphocytes; Lymphocytes T; Lymphoma; Lymphomas; Microscopy; Oncology; Physiological aspects; Serial murders; T cells; Tumors; United States
• ISSN: 1558-8238; 0021-9738; 1558-8238
• DOI: 10.1172/JCI159402

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.