Understanding the relationship between tumor and peripheral immune environments could allow longitudinal immune monitoring in cancer. Here, we examined whether T cells that share the same TCRαβ and are found in both tumor and blood can be interrogated to gain insight into the ongoing tumor T cell response. Paired transcriptome and TCRαβ repertoire of circulating and tumor-infiltrating T cells were analyzed at the single-cell level from matched tumor and blood from patients with metastatic melanoma. We found that in circulating T cells matching clonally expanded tumor-infiltrating T cells (circulating TILs), gene signatures of effector functions, but not terminal exhaustion, reflect those observed in the tumor. In contrast, features of exhaustion are displayed predominantly by tumor-exclusive T cells. Finally, genes associated with a high degree of blood–tumor TCR sharing were overexpressed in tumor tissue after immunotherapy. These data demonstrate that circulating TILs have unique transcriptional patterns that may have utility for the interrogation of T cell function in cancer immunotherapy.
Circulating clonally expanded T cells reflect functions of tumor-infiltrating T cells
Disclosures: H. Kluger reported grants from Bristol-Myers Squibb, personal fees from Bristol-Myers Squibb, grants from Merck, personal fees from Merck, grants from Apexigen, personal fees from Nektar, personal fees from iovance, personal fees from Immunocore, personal fees from Celldex, personal fees from Array Biopharma, personal fees from Elevate Bio, personal fees from Instil Bio, personal fees from Clinigen, and personal fees from Shionogi outside the submitted work. D.A. Hafler had received research funding from Bristol-Myers Squibb, Sanofi, and Genentech for work unrelated to this project. He has been a consultant over the past 10 years for Bristol-Myers Squibb, Compass Therapeutics, EMD Serono, Genentech, Juno Therapeutics, Novartis Pharmaceuticals, Proclara Biosciences, Sage Therapeutics, and Sanofi Genzyme. No other disclosures were reported.
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Liliana E. Lucca, Pierre-Paul Axisa, Benjamin Lu, Brian Harnett, Shlomit Jessel, Le Zhang, Khadir Raddassi, Lin Zhang, Kelly Olino, James Clune, Meromit Singer, Harriet M. Kluger, David A. Hafler; Circulating clonally expanded T cells reflect functions of tumor-infiltrating T cells. J Exp Med 5 April 2021; 218 (4): e20200921. doi: https://doi.org/10.1084/jem.20200921
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