Wang Yadong, Peng Ling, Zhao Ming, Xiong Yuanyuan, Xue Jianchao, Li Bowen, Huang Zhicheng, Liu Xinyu, Yang Xiaoying, Song Yang, Bing Zhongxing, Guo Chao, Tian Zhenhuan, Gao Chao, Cao Lei, Cao Zhili, Li Ji, Jiang Xu, Si Xiaoyan, Zhang Li, Li Xiaoguang, Zheng Zhibo, Song Mengmeng, Chen Rongrong, Lim Wan-Teck, Pavan Alberto, Romero Atocha, Liang Naixin, Yang Huaxia, Li Shanqing
Department of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Transl Lung Cancer Res. 2022 Sep;11(9):1936-1950. doi: 10.21037/tlcr-22-629.
Kirsten rat sarcoma viral oncogene homolog () is one of the most frequently mutated oncogenes in non-small cell lung cancer (NSCLC). The administration of immunotherapy has demonstrated significant efficacy in prolonging the overall survival of patients with mutation in recent years. However, the efficacy of immunotherapy in mutant NSCLC is variable. Analysis of T cell receptor (TCR) repertoire may contribute to a better understanding of the mechanisms behind such differential outcomes.
A total of 47 patients with mutant NSCLC were enrolled in this study. Deep sequencing of the TCR β chain complementarity-determining regions in tumor tissue and paired peripheral blood specimens was conducted. Comprehensive analysis of TCR repertoire metrics was performed with different mutation subtypes and concomitant mutations. Moreover, the associations between TCR repertoire metrics and tumor mutation burden (TMB), as well as programmed death-ligand 1 were explored, respectively.
TCR repertoire metrics, including Shannon index, Clonality, and Morisita index (MOI), showed no significant differences among different mutation subtypes. The similar results were observed between patients with tumor protein p53 () mutation and those with wild-type . In contrast, although no significant differences were found in Shannon index and Clonality, patients with KRAS/serine/threonine kinase 11 () comutation showed a significantly higher MOI compared to their wild-type counterparts (P=0.012). In addition, TCR repertoire metrics were neither associated with TMB nor programmed death-ligand 1 expression in mutant NSCLC.
This retrospective study comprehensively described the TCR repertoire in mutant NSCLC. A higher MOI represented more overlap of the TCR repertoire between tumor tissue and paired peripheral blood, indicating distinctive immunological features in NSCLC with / comutation.
Kirsten大鼠肉瘤病毒癌基因同源物（）是非小细胞肺癌（NSCLC）中最常发生突变的癌基因之一。近年来，免疫疗法在延长具有 突变患者的总生存期方面已显示出显著疗效。然而，免疫疗法在 突变NSCLC中的疗效存在差异。分析T细胞受体（TCR）库可能有助于更好地理解这种不同结果背后的机制。
本研究共纳入47例 突变NSCLC患者。对肿瘤组织和配对的外周血标本中的TCR β链互补决定区进行深度测序。对不同的 突变亚型和伴随突变进行TCR库指标的综合分析。此外，分别探讨了TCR库指标与肿瘤突变负荷（TMB）以及程序性死亡配体1之间的关联。
TCR库指标，包括香农指数、克隆性和森下指数（MOI），在不同的 突变亚型之间没有显著差异。在肿瘤蛋白p53（）突变患者和野生型 患者之间也观察到了类似的结果。相比之下，虽然在香农指数和克隆性方面没有发现显著差异，但与 野生型患者相比，伴有KRAS/丝氨酸/苏氨酸激酶11（）共突变的患者MOI显著更高（P = 0.012）。此外，在 突变NSCLC中，TCR库指标与TMB或程序性死亡配体1表达均无关联。
这项回顾性研究全面描述了 突变NSCLC中的TCR库。较高的MOI代表肿瘤组织和配对外周血之间TCR库的重叠更多，表明在伴有 / 共突变的NSCLC中具有独特的免疫特征。
