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.
Highlights
Adaptive immune responses against tumors are promising prognostic indicators for multiple cancers [1]
A significantly higher T cell receptors (TCRs) 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)
To assess the TCR repertoire in the tumor tissues and normal tissues of patients with lung cancer, we obtained RNA from 30 paired specimens isolated from the 15 patients and performed TCRb sequencing by amplifying the TCRb complementarity determining region 3 (CDR3) region, a method that we had previously used [15,18]
Summary
Adaptive immune responses against tumors are promising prognostic indicators for multiple cancers [1]. T cells infiltrating the tumor microenvironment and their corresponding receptors play vital roles in adaptive immune responses. T cell responses to cancer cells depend largely on the affinity between T cell receptors (TCRs) and peptide-major histocompatibility complex (pMHC). TCR diversity is characterized by recombination of the V/J gene segments of the TCRa and V/D/J gene segments of the TCRb. The recombination takes place in complementarity determining region 3 (CDR3) domain of TCR [3,4]. Characterizing the connection between cancer cells and the host adaptive immune system, especially pertaining to the TCR CDR3 domain, is vital for understanding tumor immunology, for identifying therapeutic targets and monitoring immunotherapy responses [5]
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