Local mutational diversity drives intratumoral immune heterogeneity in non-small cell lung cancer assessment of CD8+ TIL and PD-L1 expression

Author:Jia Q,Wu W,Wang Y, et al.


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.

PMID: 30560866

PMCID: PMC6299138

DOI: 10.1038/s41467-018-07767-w