RAF Inhibitor Therapy Promotes Melanocytic Antigen Expression and Enhanced Anti-Tumor Immunity in Melanoma

Melanoma remains a major cause of morbidity and mortality worldwide, however tremendous advances have been made in its treatment over the past several years. The discovery of genomic alterations that contribute to oncogenicity has ushered in a new era of molecularly-targeted therapy. Importantly, over half of melanomas harbor a mutation in the BRAF gene that leads to constitutive signaling down the MAPK pathway and multiple subsequent deleterious effects. Pharmacologic agents targeting this mutation have been developed and several are now FDA-approved, having yielded high response rates to therapy although these are tempered by a short duration of response. Multiple molecular mechanisms of resistance have been identified; however until recently few studies had delved into the immune effects of BRAF inhibitors. The effect of BRAF inhibition on anti-tumor immunity will be discussed herein, as will potential implications of these findings in the treatment of melanoma.