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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / genetics*
  • Antigens, Neoplasm / immunology
  • Biopsy
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / immunology*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • DNA Mutational Analysis
  • Gene Expression Profiling
  • Humans
  • Lung / pathology
  • Lung Neoplasms / genetics
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / pathology
  • Mutation
  • T-Lymphocytes / immunology*
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology*
  • Whole Exome Sequencing

Substances

  • Antigens, Neoplasm