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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

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机构: [1]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. [2]Lung Cancer Center/Lung Cancer Institute West China Hospital, Sichuan University Chengdu Sichuan China. [3]Geneplus-Beijing Institute Beijing China. [4]Departments of Bioinformatics and Computational Biology University of Texas MD Anderson Cancer Center Houston Texas USA. [5]Department of Thoracic/Head and Neck Medical Oncology University of Texas MD Anderson Cancer Center Houston Texas USA. [6]Department of Pulmonary and Critical Care Medicine West China Hospital, West China School of Medicine, Sichuan University Chengdu Sichuan China. [7]Department of Genomic Medicine University of Texas MD Anderson Cancer Center Houston Texas USA. [8]Lung Cancer Genomics Program University of Texas MD Anderson Cancer Center Houston Texas USA. [9]Lung Cancer Interception Program University of Texas MD Anderson Cancer Center Houston Texas USA.
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关键词: advanced non–small cell lung cancer clonality immunotherapy T-cell receptors tumor mutational burden

摘要:
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.© 2024 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.

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出版当年[2023]版:
大类 | 3 区 医学
小类 | 3 区 医学:研究与实验
最新[2023]版:
大类 | 3 区 医学
小类 | 3 区 医学:研究与实验
第一作者:
第一作者机构: [1]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. [2]Lung Cancer Center/Lung Cancer Institute West China Hospital, Sichuan University Chengdu Sichuan China.
通讯作者:
通讯机构: [1]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. [2]Lung Cancer Center/Lung Cancer Institute West China Hospital, Sichuan University Chengdu Sichuan China. [5]Department of Thoracic/Head and Neck Medical Oncology University of Texas MD Anderson Cancer Center Houston Texas USA. [7]Department of Genomic Medicine University of Texas MD Anderson Cancer Center Houston Texas USA. [8]Lung Cancer Genomics Program University of Texas MD Anderson Cancer Center Houston Texas USA. [9]Lung Cancer Interception Program University of Texas MD Anderson Cancer Center Houston Texas USA. [*1]Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, Precision Medicine Key Laboratory of Sichuan Province, Lung Cancer Center/Lung Cancer Institute, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China [*2]Department of Thoracic/Head and Neck Medical Oncology, Department of Genomic Medicine, Lung Cancer Genomics Program, Lung Cancer Interception Program, University of Texas MD Anderson Cancer Center, Houston/United States of America, Houston, TX 77030, USA.
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