Relationship between T cell receptor clonotype and PD‐1 expression of tumor‐infiltrating lymphocytes in colorectal cancer

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. When CTLs infiltrate into primary tumor or metastasis, expression of PD‐1 is determined by the property of TCR expressed on TILs. Here, TCR1‐expressing CTL1s express PD‐1, and TCR2‐expressing CTL2s express no PD‐1 not only in primary tumor but also in metastasis.