The combination of tumor mutational burden and T‐cell receptor repertoire predicts the response to immunotherapy in patients with advanced non–small cell lung cancer
Yalun Li,
Liyan Ji,
Yingqian Zhang,
Jiexin Zhang,
Alexandre Reuben,
Hao Zeng,
Qin Huang,
Qi Wei,
Sihan Tan,
Xuefeng Xia,
Weimin Li,
Jianjun Zhang,
Panwen Tian
Affiliations
Yalun Li
Department of Pulmonary and Critical Care Medicine State Key Laboratory of Respiratory Health and Multimorbidity West China Hospital of Sichuan University, Precision Medicine Key Laboratory of Sichuan Province Chengdu Sichuan China
Liyan Ji
Geneplus‐Beijing Institute Beijing China
Yingqian Zhang
Geneplus‐Beijing Institute Beijing China
Jiexin Zhang
Departments of Bioinformatics and Computational Biology University of Texas MD Anderson Cancer Center Houston Texas USA
Alexandre Reuben
Department of Thoracic/Head and Neck Medical Oncology University of Texas MD Anderson Cancer Center Houston Texas USA
Hao Zeng
Department of Pulmonary and Critical Care Medicine West China Hospital, West China School of Medicine, Sichuan University Chengdu Sichuan China
Qin Huang
Department of Pulmonary and Critical Care Medicine West China Hospital, West China School of Medicine, Sichuan University Chengdu Sichuan China
Qi Wei
Department of Pulmonary and Critical Care Medicine West China Hospital, West China School of Medicine, Sichuan University Chengdu Sichuan China
Sihan Tan
Department of Pulmonary and Critical Care Medicine West China Hospital, West China School of Medicine, Sichuan University Chengdu Sichuan China
Xuefeng Xia
Geneplus‐Beijing Institute Beijing China
Weimin Li
Department of Pulmonary and Critical Care Medicine State Key Laboratory of Respiratory Health and Multimorbidity West China Hospital of Sichuan University, Precision Medicine Key Laboratory of Sichuan Province Chengdu Sichuan China
Jianjun Zhang
Department of Thoracic/Head and Neck Medical Oncology University of Texas MD Anderson Cancer Center Houston Texas USA
Panwen Tian
Department of Pulmonary and Critical Care Medicine State Key Laboratory of Respiratory Health and Multimorbidity West China Hospital of Sichuan University, Precision Medicine Key Laboratory of Sichuan Province Chengdu Sichuan China
Abstract Tumor mutational burden (TMB) and T‐cell receptor (TCR) might predict the response to immunotherapy in patients with non–small cell lung cancer (NSCLC). However, the predictive value of the combination of TMB and TCR was not clear. Targeted DNA and TCR sequencing were performed on tumor biopsy specimens. We combined TMB and TCR diversity into a TMB‐and‐TCR (TMR) score using logistic regression. In total, 38 patients with advanced NSCLC were divided into a discovery set (n = 17) and validation set (n = 21). A higher TMR score was associated with better response and longer progression‐free survival to immunotherapy in both the discovery set and validation set. The performance of TMR score was confirmed in the two external validation cohorts of 225 NSCLC patients and 306 NSCLC patients. Tumors with higher TMR scores were more likely to combine with LRP1B gene mutation (p = 0.027) and top 1% CDR3 sequences (p = 0.001). Furthermore, LRP1B allele frequency was negatively correlated with the top 1% CDR3 sequences (r = –0.55, p = 0.033) and positively correlated with tumor shrinkage (r = 0.68, p = 0.007). The TMR score could serve as a potential predictive biomarker for the response to immunotherapy in advanced NSCLC.
