Spatial heterogeneity of the T cell receptor repertoire reflects the mutational landscape in lung cancer.

ABSTRACT: Somatic mutations together with immunoediting drive extensive heterogeneity within non-small-cell lung cancer (NSCLC). Herein we examine heterogeneity of the T cell antigen receptor (TCR) repertoire. The number of TCR sequences selectively expanded in tumors varies within and between tumors and correlates with the number of nonsynonymous mutations. Expanded TCRs can be subdivided into TCRs found in all tumor regions (ubiquitous) and those present in a subset of regions (regional). The number of ubiquitous and regional TCRs correlates with the number of ubiquitous and regional nonsynonymous mutations, respectively. Expanded TCRs form part of clusters of TCRs of similar sequence, suggestive of a spatially constrained antigen-driven process. CD8⁺ tumor-infiltrating lymphocytes harb

SUBMITTER: Joshi K 

PROVIDER: S-EPMC6890490 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature