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

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.

Comprehensive immune characterization and T‐cell receptor repertoire heterogeneity of retroperitoneal liposarcoma

“…In addition, although the intratumoral TCR repertoires were less heterogeneous than the differences between tumor and blood, the median pairwise intratumoral TCR repertoires overlap was 0.38, and only 35 of 125 pairwise overlaps were 0.5 or higher. These results suggested a larger heterogeneity in RLPS than in other tumors . Analyses of TCR repertoires showed that ubiquitous sequences were rare across different sites of a single tumor, which also indicated a great spatial heterogeneity within RLPS.…”

Characteristics and prognostic significance of profiling the peripheral blood T‐cell receptor repertoire in patients with advanced lung cancer

“…To our knowledge, no previous study has systematically analyzed the characteristics and clinical significance of the TCR repertoire in the peripheral blood of patients with advanced lung cancer. Furthermore, results from dynamic measurements may be more accurate due to the heterogeneity of anticancer immunity within tumors, which constantly changes over time …”

“…Furthermore, results from dynamic measurements may be more accurate due to the heterogeneity of anticancer immunity within tumors, which constantly changes over time. 7,15,28 In this study, we analyzed the TCR repertoire of peripheral blood cells from patients with advanced lung cancer and healthy controls. These two groups showed differing TCR repertoires in terms of CDR3 clonotype, diversity, V/J segment usage, and sequence.…”

“…Our knowledge of the TCR patterns in lung cancer is very limited. The TCR repertoire is heterogeneous, differing between regions within the same tumor in lung cancer and many other malignancies . Furthermore, tumor tissue is difficult to obtain and dynamically monitor, especially in patients with advanced disease.…”

“…The TCR repertoire is heterogeneous, differing between regions within the same tumor in lung cancer and many other malignancies. 13,15,[24][25][26][27][28] Furthermore, tumor tissue is difficult to obtain and dynamically monitor, especially in patients with advanced disease. The use of blood samples is an attractive alternative to overcome these problems.…”