TCR repertoire intratumor heterogeneity of CD4+ and CD8+ T cells in centers and margins of localized lung adenocarcinomas

International Journal of Cancer. Journal International Du Cancer
Chaoting ZhangZheming Lu

Abstract

Intratumor heterogeneity (ITH) of T cell receptor (TCR) repertoire in different T-cell subsets and locations in lung adenocarcinomas was unclear. Here, we investigated percentages and TCR repertoire of freshly isolated CD4+ and CD8+ tumor infiltrating lymphocytes (TILs) in tumor centers and margins by flow cytometry on 80 tumor samples from 20 patients and high-throughput TCR sequencing on 27 and 25 samples of CD4+ and CD8+ TILs from seven patients. Our results demonstrated that amount and TCR repertoire diversity of CD4+ TILs were significantly higher than those of CD8+ TILs and moreover substantial ITH regarding amount and TCR repertoire of CD4+ and CD8+ TILs were observed. Additionally, ITH of CD4/CD8 T-cell ratio and CD8+ TIL repertoire across center regions was lower than that across margin regions. The amount and TCR repertoire ITH of CD4+ and CD8+ TILs and mean clonality of CD8+ TILs in tumor centers were associated with relapse. Our study provides insights into amount and TCR repertoire ITH of CD4+ and CD8+ TILs in tumor centers and margins as well as corresponding association with prognosis in lung adenocarcinoma patients, suggesting potential clinical significance of TCR repertoire.

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Citations

Jan 22, 2019·International Journal of Cancer. Journal International Du Cancer·Yang-Yang LiuLi Liu
Sep 11, 2020·Bioscience Trends·Changbo Sun, Shun Xu
Mar 3, 2021·Journal of Experimental & Clinical Cancer Research : CR·Yijie ZhangWei Xiong
Feb 26, 2021·Seminars in Cancer Biology·Yin WuCharles Swanton
Apr 14, 2021·The Journal of Pathology·Mark M KockxHartmut Koeppen

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