BRAF and MEK inhibitors differentially affect nivolumab-induced T cell activation by modulating the TCR and AKT signaling pathways.

ABSTRACT: Immune checkpoint inhibitors (ICIs) such as the anti-PD-1 antibody Nivolumab, achieve remarkable clinical efficacy in patients with late stage cancers. However, only a small subset of patients benefit from this therapy. Numerous clinical trials are underway testing whether combining ICIs with other anti-cancer therapies can increase this response rate. For example, anti-PD-1/PD-L1 therapy combined with MAP kinase inhibition using BRAF inhibitors (BRAFi) and/or MEK inhibitors (MEKi) are in development for treatment of late stage melanomas. However, the benefits and underlying mechanisms of these combinatorial therapies remain unclear. In the current study, we assess the effects of MAPK inhibition on Nivolumab-induced T cell responses. Using an in vitro mixed lymphocyte reaction assay

SUBMITTER: Yue P 

PROVIDER: S-EPMC6287803 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature