Inhibition of MEK with trametinib enhances the efficacy of anti-PD-L1 inhibitor by regulating anti-tumor immunity in head and neck squamous cell carcinoma.

ABSTRACT: Major histocompatibility complex (MHC) class I downregulation is the primary immune evasion mechanism associated with failure in anti-PD-1/PD-L1 blockade therapies for cancer. Here, we examined the role of MEK signaling pathway inhibition in head and neck squamous cell carcinoma (HNSCC) both in vitro and in vivo. We found that trametinib, a small molecule inhibitor of MEK, significantly enhanced MHC class I and PD-L1 expression in human HNSCC cell lines, and this occurred via STAT3 activation. Trametinib also further upregulated the increase in CXCL9 and CXCL10 expression caused by IFN-γ in HNSCC cells, which is associated with T cell infiltration in tumor tissues. Finally, we evaluated the therapeutic efficacy of trametinib combined with an anti-PD-L1 monoclonal antibody

SUBMITTER: Kang SH 

PROVIDER: S-EPMC6287796 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature