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.
T细胞和T细胞受体(TCR)在抗肿瘤的适应性免疫反应中发挥重要作用。TCR负责特异性的识别抗原,其重排过程中产生的高度可变的互补决定区3（complementary determining region 3，CDR3）序列是识别TCR特异性的主要标记。采用二代测序的方法评估TCRβ链的CDR3区可以很大程度上反映T细胞的克隆组成及其多样性，进而评估机体的抗肿瘤免疫反应，这就是通常所说的T细胞免疫组库。目前关于肺癌组织的T细胞免疫组库研究较少，本研究中我们对比分析了15例肺癌患者的肿瘤组织和癌旁正常肺组织的T细胞免疫组库。基于我们的研究结果，肺癌组织和癌旁正常肺组织的总体T细胞克隆分布相似；而正常肺组织相比于肺癌组织具有更高比例的高扩增克隆（0.021% ± 0.002% vs. 0.016% ± 0.001%，P = 0.0054，Wilcoxon signed rank test）。此外，我们发现肿瘤组织的TCR多样性显著高于正常肺组织（431.37 ± 305.96 vs. 166.20 ± 101.58，P = 0.0075，Mann-Whitney U test）。年轻的肺癌患者TCR的多样性要显著高于老年患者（640.7 ± 295.3 vs. 291.8 ± 233.6, P = 0.036, Mann-Whitney U test），而肿瘤组织中更高的TCR多样性与患者的不良预后显著相关。通过此项研究，我们比较分析了肺癌患者肿瘤组织和配对的正常肺组织的T细胞免疫组库特征，证明了肺癌患者间存在不同的T细胞免疫微环境，同时发现肺癌组织的TCR多样性与肺癌患者临床预后之间存在关联，提示可能通过检测肺癌患者的组织T细胞免疫组库来评价患者的预后，具有重要的临床价值。





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