Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer.

ABSTRACT: Immune checkpoint inhibitors, which unleash a patient's own T cells to kill tumors, are revolutionizing cancer treatment. To unravel the genomic determinants of response to this therapy, we used whole-exome sequencing of non-small cell lung cancers treated with pembrolizumab, an antibody targeting programmed cell death-1 (PD-1). In two independent cohorts, higher nonsynonymous mutation burden in tumors was associated with improved objective response, durable clinical benefit, and progression-free survival. Efficacy also correlated with the molecular smoking signature, higher neoantigen burden, and DNA repair pathway mutations; each factor was also associated with mutation burden. In one responder, neoantigen-specific CD8+ T cell responses paralleled tumor regression, suggesting that anti-P

SUBMITTER: Rizvi NA 

PROVIDER: S-EPMC4993154 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature