Relationship between T cell receptor clonotype and PD‐1 expression of tumor‐infiltrating lymphocytes in colorectal cancer
- 22 May 2020
- journal article
- research article
- Published by Wiley in European Journal of Immunology
- Vol. 50 (10), 1580-1590
- https://doi.org/10.1002/eji.201948399
Abstract
Adoptive T cell therapy using tumor-specific T cells or TCR-modified T cells is a promising next-generation immunotherapy. The major source of tumor-reactive T cells is PD-1+ tumor-infiltrating lymphocytes (TILs). In contrast, PD-1− TILs have received little attention. Here, we analyzed the TCR-β repertoires of PD-1− and PD-1+ CD8+ TILs derived from colorectal cancer and breast cancer. Approximately 40–60% of the PD-1+ population consisted of oligoclonal populations in both colorectal cancer and breast cancer. In contrast, approximately 37% of the PD-1− population consisted of an oligoclonal population in colorectal cancer, whereas 14% of them were oligoclonal in breast cancer. In colorectal cancer, the TCR repertoires of PD-1−CD8+ TILs and PD-1+CD8+ TILs hardly overlapped. Interestingly, clonally expanded CD8+ TILs in primary tumors and the metastases expressing the same clonotypic TCR showed the same phenotype regarding the PD-1-expression. These results suggest that the intrinsic properties of TCRs determine the fate of TILs in terms of whether they become PD-1+ or PD-1− in the tumor microenvironment. Further functional analysis of TCRs in TILs will allow us to better understand the regulatory mechanisms for PD-1 expression on TILs and may contribute to tumor immunotherapy.Keywords
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