Resistance mechanisms to PD-1 inhibition in melanoma

Immune checkpoint inhibition using antibodies against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death 1 (PD-1) have substantially improved treatment outcomes for patients with advanced melanoma. (1-3). However, despite the remarkable durability of objective responses induced by these treatments, progressive disease occurs in about a quarter of the patients within the first 3 years (4). Understanding the molecular mechanisms of acquired resistance by focused comparison of biopsy samples from paired baseline and relapsing lesions should open strategies for the rational design of salvage therapies and may guide mechanistic biomarker studies for the identification of patients, before the initiation of treatment, who are unlikely to have a response.