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Nat Commun. 2018 Dec 18;9(1):5361. doi: 10.1038/s41467-018-07767-w.

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

Jia Q1,2, Wu W3, Wang Y4, Alexander PB5, Sun C1,2, Gong Z1,2, Cheng JN1,2,6, Sun H4, Guan Y4, Xia X4,7, Yang L4, Yi X4, Wan YY8, Wang H3, He J9, Futreal PA10, Li QJ11,12, Zhu B13,14.

Author information

1
Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.
2
Chongqing Key Laboratory of Tumor Immunotherapy, Chongqing, 400037, China.
3
Department of Cardiothorathic Surgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.
4
Geneplus-Beijing Institute, Beijing, 102206, China.
5
Department of Immunology, Duke University Medical Center, Durham, 27710, NC, USA.
6
Biomedical Analysis Center, Third Military Medical University, Chongqing, 400038, China.
7
Houston Methodist Research Institute, Houston, 77030, TX, USA.
8
Department of Microbiology and Immunology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, 27514, NC, USA.
9
GeneCast Biotechnology Co., Ltd, Beijing, 102206, China.
10
Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
11
Department of Immunology, Duke University Medical Center, Durham, 27710, NC, USA. Qi-Jing.Li@Duke.edu.
12
Biomedical Analysis Center, Third Military Medical University, Chongqing, 400038, China. Qi-Jing.Li@Duke.edu.
13
Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China. bo.zhu@tmmu.edu.cn.
14
Chongqing Key Laboratory of Tumor Immunotherapy, Chongqing, 400037, China. bo.zhu@tmmu.edu.cn.

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.

PMID:
30560866
PMCID:
PMC6299138
DOI:
10.1038/s41467-018-07767-w
[Indexed for MEDLINE]
Free PMC Article

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