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

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 () and Bo Zhu ()
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Qingzhu Jia: Third Military Medical University
Wei Wu: Third Military Medical University
Yuqi Wang: Geneplus-Beijing Institute
Peter B. Alexander: Duke University Medical Center
Chengdu Sun: Third Military Medical University
Zhihua Gong: Third Military Medical University
Jia-Nan Cheng: Third Military Medical University
Huaibo Sun: Geneplus-Beijing Institute
Yanfang Guan: Geneplus-Beijing Institute
Xuefeng Xia: Geneplus-Beijing Institute
Ling Yang: Geneplus-Beijing Institute
Xin Yi: Geneplus-Beijing Institute
Yisong Y. Wan: University of North Carolina at Chapel Hill
Haidong Wang: Third Military Medical University
Ji He: GeneCast Biotechnology Co., Ltd
P. Andrew Futreal: The University of Texas MD Anderson Cancer Center
Qi-Jing Li: Duke University Medical Center
Bo Zhu: Third Military Medical University

Nature Communications, 2018, vol. 9, issue 1, 1-10

Abstract: Abstract 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.

Date: 2018
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DOI: 10.1038/s41467-018-07767-w

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