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

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.