The MEK inhibitor selumetinib complements CTLA-4 blockade by reprogramming the tumor immune microenvironment.

ABSTRACT:

Background

T-cell checkpoint blockade and MEK inhibitor combinations are under clinical investigation. Despite progress elucidating the immuno-modulatory effects of MEK inhibitors as standalone therapies, the impact of MEK inhibition on the activity of T-cell checkpoint inhibitors remains incompletely understood. Here we sought to characterize the combined effects of MEK inhibition and anti-CTLA-4 mAb (anti-CTLA-4) therapy, examining effects on both T-cells and tumor microenvironment (TME).

Methods

In mice, the effects of MEK inhibition, via selumetinib, and anti-CTLA-4 on immune responses to keyhole limpet haemocyanin (KLH) immunization were monitored using ex vivo functional assays with splenocytes. In a KRAS-mutant CT26 mouse colorectal cancer model, the impact on the tum

SUBMITTER: Poon E 

PROVIDER: S-EPMC5557252 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature