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

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.

SUBMITTER: Jia Q 

PROVIDER: S-EPMC6299138 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature