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

被引：0
作者：
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
机构：
[1] Third Military Medical University,Institute of Cancer, Xinqiao Hospital
[2] Chongqing Key Laboratory of Tumor Immunotherapy,Department of Cardiothorathic Surgery, Southwest Hospital
[3] Third Military Medical University,Department of Immunology
[4] Geneplus-Beijing Institute,Biomedical Analysis Center
[5] Duke University Medical Center,Department of Microbiology and Immunology, Lineberger Comprehensive Cancer Center
[6] Third Military Medical University,Department of Genomic Medicine
[7] Houston Methodist Research Institute,undefined
[8] University of North Carolina at Chapel Hill,undefined
[9] GeneCast Biotechnology Co.,undefined
[10] Ltd,undefined
[11] The University of Texas MD Anderson Cancer Center,undefined
来源：
Nature Communications | / 9卷
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摘要：
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 of 15 patients with non-small cell lung cancer (NSCLC). This revealed that the immune microenvironment has high spatial heterogeneity such that intratumoral regional variation is as large as inter-personal variation. While the local total mutational burden (TMB) is associated with local T-cell clonal expansion, local anti-tumor cytotoxicity does not directly correlate with neoantigen abundance. Together, these findings caution against that immunological signatures can be predicted solely from TMB or microenvironmental analysis from a single locus biopsy.
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