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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • 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

Published Date

  • December 18, 2018

Published In

Volume / Issue

  • 9 / 1

Start / End Page

  • 5361 -

PubMed ID

  • 30560866

Pubmed Central ID

  • PMC6299138

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-018-07767-w


  • eng

Conference Location

  • England