MEK inhibition, alone or in combination with BRAF inhibition, impairs multiple functions of isolated normal human lymphocytes and dendritic cells

Introduction Combination therapy with BRAF and MEK inhibition is currently in clinical development for the treatment of BRAF mutated malignant melanoma. BRAF inhibitors are associated with enhanced antigen-specific T-lymphocyte recognition in vivo. Consequently BRAF inhibition has been proposed as pro-immunogenic and there has been considerable enthusiasm for combining BRAF inhibition with immunotherapy. MEK inhibitors inhibit ERK phosphorylation regardless of BRAF mutational status and have been reported to impair T-lymphocyte and dendritic cell function. In this study we investigate the effects on isolated T-lymphocytes and monocyte-derived dendritic cells (moDCs) of a MEK and BRAF inhibitor combination currently being evaluated in a randomized controlled clinical trial.