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
This publication has 49 references indexed in Scilit:
- MHC Multimer-Guided and Cell Culture-Independent Isolation of Functional T Cell Receptors from Single Cells Facilitates TCR Identification for ImmunotherapyPLOS ONE, 2013
- Unbiased Analysis of TCRα/β Chains at the Single-Cell Level in Human CD8+ T-Cell SubsetsPLOS ONE, 2012
- Analysis of the Paired TCR α- and β-chains of Single Human T CellsPLOS ONE, 2012
- Retaining cell–cell contact enables preparation and culture of spheroids composed of pure primary cancer cells from colorectal cancerProceedings of the National Academy of Sciences of the United States of America, 2011
- Paired analysis of TCRα and TCRβ chains at the single-cell level in miceJCI Insight, 2011
- Tumor antigen–specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impairedBlood, 2009
- Activation-induced expression of CD137 permits detection, isolation, and expansion of the full repertoire of CD8+ T cells responding to antigen without requiring knowledge of epitope specificitiesBlood, 2007
- Adoptive T cell therapy for cancer in the clinicJCI Insight, 2007
- Cancer Regression in Patients After Transfer of Genetically Engineered LymphocytesScience, 2006
- Reconstitution of paired T cell receptor α- and β-chains from microdissected single cells of human inflammatory tissuesProceedings of the National Academy of Sciences of the United States of America, 2006