TCR of lung

Lung cancer is the leading cause of cancer-related deaths worldwide, and its occurrence is related to the accumulation of gene mutations and immune escape of the tumor. Sequencing of the T cell receptor (TCR) repertoire can reveal the immunosurveillance status of the tumor microenvironment, which is related to tumor escape and immunotherapy. This study aimed to determine the characteristics and clinical significance of the TCR repertoire in lung cancer. To comprehensively profile the TCR repertoire, results from high-throughput sequencing of samples from 93 Chinese lung cancer patients were analyzed. We found that the TCR clonality of tissues was related to smoking, with higher clonality in patients who had quit smoking for less than 1 year. As expected, TCR clonality was correlated with stages, and stage IV patients showed higher clonality than others. The correlation between TCR repertoire and epidermal growth factor receptor (EGFR) status was also investigated. EGFR non-L858R patients showed higher clonality and lower Shannon index than others, including EGFR L858R and EGFR wild-type patients. Further, we analyzed the TCR similarity metrics, that is, the TCR shared between postoperative peripheral blood and tissue, of patients with non-distant metastasis lung cancer. A similar trend was found, with EGFR L858R patients having lower OLI and MOI. Moreover, OLI showed a positive correlation with several clinical characteristics, including the tumor mutational burden of tissues and maximum somatic allele frequency of blood; and OLI showed negative correlation with ratio of CD4+CD28+/CD4+ and ratio of CD8+CD28+/CD8+. In conclusion, TCR clonality and TCR similarity metrics were correlated with clinical characteristics of lung cancer patients, and differences in TCR clonality, Shannon index, and OLI across EGFR subtypes provide information for the potential understanding of the different response to immunotherapy in patients with different EGFR mutations.