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

Publication ,  Journal Article
Jia, Q; Wu, W; Wang, Y; Alexander, PB; Sun, C; Gong, Z; Cheng, J-N; Sun, H; Guan, Y; Xia, X; Yang, L; Yi, X; Wan, YY; Wang, H; He, J ...
Published in: Nat Commun
December 18, 2018
Published version (DOI) Link to item

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.

Duke Scholars

Qi-Jing Li
Author Qi-Jing Li Integrative Immunobiology
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Published In

Nat Commun

DOI

10.1038/s41467-018-07767-w

EISSN

2041-1723

Publication Date

December 18, 2018

Volume

9

Issue

1

Start / End Page

5361

Location

England

Related Subject Headings

  • Tumor Microenvironment
  • T-Lymphocytes
  • Mutation
  • Lung Neoplasms
  • Lung
  • Humans
  • Gene Expression Profiling
  • Exome Sequencing
  • DNA Mutational Analysis
  • Carcinoma, Non-Small-Cell Lung
 

Citation

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MLA
NLM
Jia, Q., Wu, W., Wang, Y., Alexander, P. B., Sun, C., Gong, Z., … Zhu, B. (2018). Local mutational diversity drives intratumoral immune heterogeneity in non-small cell lung cancer. Nat Commun, 9(1), 5361. https://doi.org/10.1038/s41467-018-07767-w
Jia, Qingzhu, Wei Wu, Yuqi Wang, Peter B. Alexander, Chengdu Sun, Zhihua Gong, Jia-Nan Cheng, et al. “Local mutational diversity drives intratumoral immune heterogeneity in non-small cell lung cancer.” Nat Commun 9, no. 1 (December 18, 2018): 5361. https://doi.org/10.1038/s41467-018-07767-w.
Jia Q, Wu W, Wang Y, Alexander PB, Sun C, Gong Z, et al. Local mutational diversity drives intratumoral immune heterogeneity in non-small cell lung cancer. Nat Commun. 2018 Dec 18;9(1):5361.
Jia, Qingzhu, et al. “Local mutational diversity drives intratumoral immune heterogeneity in non-small cell lung cancer.” Nat Commun, vol. 9, no. 1, Dec. 2018, p. 5361. Pubmed, doi:10.1038/s41467-018-07767-w.
Jia Q, Wu W, Wang Y, Alexander PB, Sun C, Gong Z, Cheng J-N, Sun H, Guan Y, Xia X, Yang L, Yi X, Wan YY, Wang H, He J, Futreal PA, Li Q-J, Zhu B. Local mutational diversity drives intratumoral immune heterogeneity in non-small cell lung cancer. Nat Commun. 2018 Dec 18;9(1):5361.

Published In

Nat Commun

DOI

10.1038/s41467-018-07767-w

EISSN

2041-1723

Publication Date

December 18, 2018

Volume

9

Issue

1

Start / End Page

5361

Location

England

Related Subject Headings

  • Tumor Microenvironment
  • T-Lymphocytes
  • Mutation
  • Lung Neoplasms
  • Lung
  • Humans
  • Gene Expression Profiling
  • Exome Sequencing
  • DNA Mutational Analysis
  • Carcinoma, Non-Small-Cell Lung