Activation of CD8⁺ T Cells Contributes to Antitumor Effects of CDK4/6 Inhibitors plus MEK Inhibitors.

ABSTRACT: Concurrent MEK and CDK4/6 inhibition shows promise in clinical trials for patients with advanced-stage mutant BRAF/NRAS solid tumors. The effects of CDK4/6 inhibitor (CDK4/6i) in combination with BRAF/MEK-targeting agents on the tumor immune microenvironment are unclear, especially in melanoma, for which immune checkpoint inhibitors are effective in approximately 50% of patients. Here, we show that patients progressing on CDK4/6i/MEK pathway inhibitor combinations exhibit T-cell exclusion. We found that MEK and CDK4/6 targeting was more effective at delaying regrowth of mutant BRAF melanoma in immunocompetent versus immune-deficient mice. Although MEK inhibitor (MEKi) treatment increased tumor immunogenicity and intratumoral recruitment of CD8⁺ T cells, the

SUBMITTER: Teh JLF 

PROVIDER: S-EPMC7484433 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature