The evolution of T-cell receptor repertoire in different stages of non-small cell lung cancer

Autor: Ziqi Jia, Yadong Wang, Xiaoying Yang, Pancheng Wu, Yanyu Wang, Yang Song, Huihui Xu, Dejian Gu, Rongrong Chen, Jin Li, Xuefeng Xia, Zhongxing Bing, Lei Cao, Zhili Cao, Peng Liu, Huaxia Yang, Shanqing Li, Naixin Liang
Rok vydání: 2020
Předmět:
Popis: Background The intricate relationship between the tumor and host was not well understood, and antigen-specific T cell is fundamental in understanding the interaction. TCR repertoire analysis which described TCR clonotypes and TCR numbers has shown that TCRs with high frequency was tumor-specific T cells, while others might be ‘bystander’ T cells within tumors. However, how these “expanded” tumor-specific T cells was selected during the tumor development was not clear. Methods We retrospectively analyzed TCR sequencing and mutation sequencing results from 144 non-small cell lung cancer (NSCLC) patients. Results A rich TCR repertoire comprising thousands of different TCR sequences was identified in all stages of NSCLC, with most TCR clonotypes presented at low frequency. Interestingly, Stage IV NSCLC tumors contain more expanded TCRs as compared to earlier stages, however, lymph node metastasis or tumor size had little impact on expanded TCRs. Moreover, accumulation of mutations did not significantly change the number of TCR clonotypes, however, EGFR mutant patients had significantly lower while KRAS mutant patients had significantly higher number of TCR clonotypes especially in terms of those “expanded” TCRs. Conclusions In summary, T cells in the tumor microenvironment were gradually activated with tumor development. Critical events such as distal metastases and generation of EGFR or KRAS mutations might be the major factors affecting the changing of tumor-specific T cells in the tumor microenvironment.
Databáze: OpenAIRE