title: Anti-PD-1 therapy in melanoma.
abstract: Immune-regulatory mechanisms are used by cancer to hide from the immune system. Advances and in-depth understanding of the biology of melanoma and its interaction with the immune system have led to the development of some of antagonistic antibodies to the programmed death 1 pathway (PD-1) and one of its ligands, programmed death ligand 1 (PD-L1), which are demonstrating high clinical benefit rates and tolerability. Blocking the immune-regulatory checkpoints that limit T-cell responses to melanoma upon PD-1/PD-L1 modulation has provided clinically validated targets for cancer immunotherapy. Combinations with other anti-melanoma agents may result in additional benefits. Nivolumab, pembrolizumab (formerly known as MK-3475 and lambrolizumab), and pidilizumab are anti-PD-1 antibodies in clinical development for melanoma, non-small cell lung cancer, renal cell carcinoma, head and neck cancers, lymphoma, and several other cancers. Long-term survivors already have been reported with these therapies. In this review, we discuss the current state of anti-PD-1 agents, the evidence in the literature to support the combination of anti-PD-1 antibodies with other anti-cancer agents and discuss the future directions for rational design of clinical trials that keep on increasing the number of long-term survivors.
authors.affiliation: Department of Medicine, Division of Hematology-Oncology, University of California Los Angeles (UCLA), CA.
authors.forename: Blanca
authors.initials: B
authors.lastname: Homet Moreno
authors.affiliation: Department of Medicine, Division of Hematology-Oncology, University of California Los Angeles (UCLA), CA; Department of Oncology, Division of Medical Oncology and Immunotherapy, University Hospital of Siena, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Parisi
authors.affiliation: Department of Medicine, Division of Hematology-Oncology, University of California Los Angeles (UCLA), CA.
authors.forename: Lidia
authors.initials: L
authors.lastname: Robert
authors.affiliation: Department of Medicine, Division of Hematology-Oncology, University of California Los Angeles (UCLA), CA; Department of Surgery, University of California Los Angeles (UCLA), Los Angeles, CA; Department of Medical and Molecular Pharmacology, University of California Los Angeles (UCLA), Los Angeles, CA; Jonsson Comprehensive Cancer Center (JCCC) at UCLA, Los Angeles, CA. Electronic address: aribas@mednet.ucla.edu.
authors.forename: Antoni
authors.initials: A
authors.lastname: Ribas
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use; D007167:Immunotherapy; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D058990:Molecular Targeted Therapy; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D007155:Immunologic Factors; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor