Local mutational diversity drives intratumoral immune heterogeneity in non-small cell lung cancer

• DOI: 10.1038/s41467-018-07767-w
• Publication Date: 2018-12-12T10:43:52Z
• Authors: Qingzhu Jia; Wei Wu; Yuqi Wang; Peter B. Alexander; Chengdu Sun; Zhihua Gong; Jia-Nan Cheng; Huaibo Sun; Yanfang Guan; Xuefeng Xia; Ling Yang; Xin Yi; Yisong Y. Wan; Haidong Wang; Ji He; P. Andrew Futreal; Qi-Jing Li; Bo Zhu
• Keywords: 0303 health sciences; Lung Neoplasms; Science; Biopsy; Gene Expression Profiling; T-Lymphocytes; Q; DNA Mutational Analysis; Article; 3. Good health; 03 medical and health sciences; Antigens, Neoplasm; Carcinoma, Non-Small-Cell Lung; Mutation; Exome Sequencing; Tumor Microenvironment; Humans; Lung

Combining whole exome sequencing, transcriptome profiling, and T cell repertoire analysis, we investigate the spatial features of surgically-removed biopsies from multiple loci in tumor masses 15 patients with non-small lung cancer (NSCLC). This revealed that immune microenvironment has high heterogeneity such intratumoral regional variation is as large inter-personal variation. While local total mutational burden (TMB) associated T-cell clonal expansion, anti-tumor cytotoxicity does not directly correlate neoantigen abundance. Together, these findings caution against immunological signatures can be predicted solely TMB or microenvironmental analysis a single locus biopsy.