Replication stress response defects are associated with response to immune checkpoint blockade in nonhypermutated cancers.

ABSTRACT: Treatment with immune checkpoint blockade (ICB) has resulted in durable responses for a subset of patients with cancer, with predictive biomarkers for ICB response originally identified largely in the context of hypermutated cancers. Although recent clinical data have demonstrated clinical responses to ICB in certain patients with nonhypermutated cancers, previously established ICB response biomarkers have failed to accurately identify which of these patients may benefit from ICB. Here, we demonstrated that a replication stress response (RSR) defect gene expression signature, but not other proposed biomarkers, is associated with ICB response in 12 independent cohorts of patients with nonhypermutated cancer across seven tumor types, including those of the breast, prostate, kidney, and brain

SUBMITTER: McGrail DJ 

PROVIDER: S-EPMC8577990 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature