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; Bo Zhu

doi:10.1038/s41467-018-07767-w

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, Bo Zhu

Genomic Medicine

Research output: Contribution to journal › Article › peer-review

272 Scopus citations

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.

Original language	English (US)
Article number	5361
Journal	Nature communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-07767-w
State	Published - Dec 1 2018

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Jia, Q., Wu, W., Wang, Y., Alexander, P. B., Sun, C., Gong, Z., Cheng, J. N., Sun, H., Guan, Y., Xia, X., Yang, L., Yi, X., Wan, Y. Y., Wang, H., He, J., Futreal, P. A., Li, Q. J., & Zhu, B. (2018). Local mutational diversity drives intratumoral immune heterogeneity in non-small cell lung cancer. Nature communications, 9(1), Article 5361. https://doi.org/10.1038/s41467-018-07767-w

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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.",

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AU - Jia, Qingzhu

AU - Wu, Wei

AU - Wang, Yuqi

AU - Alexander, Peter B.

AU - Sun, Chengdu

AU - Gong, Zhihua

AU - Cheng, Jia Nan

AU - Sun, Huaibo

AU - Guan, Yanfang

AU - Xia, Xuefeng

AU - Yang, Ling

AU - Yi, Xin

AU - Wan, Yisong Y.

AU - Wang, Haidong

AU - He, Ji

AU - Futreal, P. Andrew

AU - Li, Qi Jing

AU - Zhu, Bo

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

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