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Multidimensional single-cell analysis identifies a role for CD2-CD58 interactions in clinical antitumor T cell responses
Gabrielle Romain, … , Sattva S. Neelapu, Navin Varadarajan
Gabrielle Romain, … , Sattva S. Neelapu, Navin Varadarajan
Published July 26, 2022
Citation Information: J Clin Invest. 2022;132(17):e159402. https://doi.org/10.1172/JCI159402.
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Research Article Immunology Oncology Article has an altmetric score of 103

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

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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.

Authors

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

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Figure 4

Prognostic role of pretreatment CD58 expression by IHC in patients with relapsed refractory LBCL treated with axi-cel.

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Prognostic role of pretreatment CD58 expression by IHC in patients with ...
(A) CD58 expression by IHC in tissue samples collected before treatment with standard-of-care axi-cel. Left panels (negative case): IHC for CD58 shows diffuse negativity of the lymphoma cells with positive internal control (bars show the depth of magnification). Right panels (positive cases): IHC for CD58 shows diffuse cytoplasmic and membranous stain with strong intensity in all lymphoma cells (bars show the depth of magnification). (B) CD58 H score according to day 90 response to standard-of-care axi-cel. Bars represent the median. CR, n = 21; PD, n = 18. P value was computed using Mann-Whitney U test. (C) PFS after standard-of-care axi-cel according to pretreatment CD58 H score (cut-off = 80). N, number. PFS was calculated using Kaplan-Meier estimates and was compared between subgroups using the log-rank test.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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