Characterization of Distinct T Cell Receptor Repertoires in Tumor and Distant Non-tumor Tissues from Lung Cancer Patients / 基因组蛋白质组与生物信息学报·英文版

ABSTRACT

T cells and T cell receptors (TCRs) play pivotal roles in adaptive immune responses against tumors. The development of next-generation sequencing technologies has enabled the analysis of the TCRβ repertoire usage. Given the scarce investigations on the TCR repertoire in lung cancer tissues, in this study, we analyzed TCRβ repertoires in lung cancer tissues and the matched distant non-tumor lung tissues (normal lung tissues) from 15 lung cancer patients. Based on our results, the general distribution of T cell clones was similar between cancer tissues and normal lung tissues; however, the proportion of highly expanded clones was significantly higher in normal lung tissues than in cancer tissues (0.021% ± 0.002% vs. 0.016% ± 0.001%, P = 0.0054, Wilcoxon signed rank test). In addition, a significantly higher TCR diversity was observed in cancer tissues than in normal lung tissues (431.37 ± 305.96 vs. 166.20 ± 101.58, P = 0.0075, Mann-Whitney U test). Moreover, younger patients had a significantly higher TCR diversity than older patients (640.7 ± 295.3 vs. 291.8 ± 233.6, P = 0.036, Mann-Whitney U test), and the higher TCR diversity in tumors was significantly associated with worse cancer outcomes. Thus, we provided a comprehensive comparison of the TCR repertoires between cancer tissues and matched normal lung tissues and demonstrated the presence of distinct T cell immune microenvironments in lung cancer patients.