IL15 Agonists Overcome the Immunosuppressive Effects of MEK Inhibitors.

ABSTRACT: Many signal transduction inhibitors are being developed for cancer therapy target pathways that are also important for the proper function of antitumor lymphocytes, possibly weakening their therapeutic effects. Here we show that most inhibitors targeting multiple signaling pathways have especially strong negative effects on T-cell activation at their active doses on cancer cells. In particular, we found that recently approved MEK inhibitors displayed potent suppressive effects on T cells in vitro However, these effects could be attenuated by certain cytokines that can be administered to cancer patients. Among them, clinically available IL15 superagonists, which can activate PI3K selectively in T lymphocytes, synergized with MEK inhibitors in vivo to elicit potent and durable antitumor resp

SUBMITTER: Allegrezza MJ 

PROVIDER: S-EPMC4873368 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature