Contraction of T cell richness in lung cancer brain metastases

Sci Rep. 2018 Feb 1;8(1):2171. doi: 10.1038/s41598-018-20622-8.

Abstract

Very little is known about how the adaptive immune system responds to clonal evolution and tumor heterogeneity in non-small cell lung cancer. We profiled the T-cell receptor β complementarity determining region 3 in 20 patients with fully resected non-small cell lung cancer primary lesions and paired brain metastases. We characterized the richness, abundance and overlap of T cell clones between pairs, in addition to the tumor mutation burden and predicted neoantigens. We found a significant contraction in the number of unique T cell clones in brain metastases compared to paired primary cancers. The vast majority of T cell clones were specific to a single lesion, and there was minimal overlap in T cell clones between paired lesions. Despite the contraction in the number of T cell clones, brain metastases had higher non-synonymous mutation burdens than primary lesions. Our results suggest that there is greater richness of T cell clones in primary lung cancers than their paired metastases despite the higher mutation burden observed in metastatic lesions. These results may have implications for immunotherapy.

Publication types

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

MeSH terms

  • Adenocarcinoma / immunology*
  • Adenocarcinoma / pathology
  • Aged
  • Brain Neoplasms / immunology*
  • Brain Neoplasms / secondary
  • Carcinoma, Non-Small-Cell Lung / immunology*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Squamous Cell / immunology*
  • Carcinoma, Squamous Cell / pathology
  • Clonal Evolution
  • Female
  • Humans
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / pathology