title: Targeting the PD1/PD-L1 axis in melanoma: biological rationale, clinical challenges and opportunities.
abstract: A dynamic interplay exists between host and tumor, and the ability of the tumor to evade immune recognition often determines the clinical course of the disease. Significant enthusiasm currently exists for a new immunotherapeutic strategy: the use of immunomodulatory monoclonal antibodies that directly enhance the function of components of the anti-tumor immune response such as T cells, or block immunologic checkpoints that would otherwise restrain effective anti-tumor immunity. This strategy is based on the evidence that development of cancer is facilitated by the dis-regulation and exploitation of otherwise physiological pathways that, under normal circumstances, down-regulate immune activation and maintain tolerance to self. Among these pathways an important role is covered by the Programmed death-1 (PD-1)/PD-Ligand (L) 1 axis. An emerging concept in cancer immunology is that inhibitory ligands such as PD-L1 are induced in response to immune attack, a mechanism termed "adaptive resistance". This potential mechanism of immune resistance by tumors suggests that therapy directed at blocking the interaction between PD-1 and PD-L1 might synergize with other treatments that enhance endogenous antitumor immunity. The anti-PD-1 strategy can be effective in several solid tumors such as renal cell carcinoma (RCC) or non-small cell lung cancer (NSCLC), however in this review we summarize the biological role of PD-1/PD-L1 on cancer by focusing our attention in the biological rationale, clinical challenges and opportunities to target the PD-1/PD-L1 axis in melanoma.
authors.affiliation: Unit of Medical Oncology, Department of Oncology and Hematology, Papa Giovanni XXIII Hospital, Bergamo, Italy. Electronic address: bmerelli@hpg23.it.
authors.forename: Barbara
authors.initials: B
authors.lastname: Merelli
authors.affiliation: Division of Pathological Anatomy, Department of Surgery and Translational Medicine, University of Florence, Italy. Electronic address: daniela.massi@unifi.it.
authors.forename: Daniela
authors.initials: D
authors.lastname: Massi
authors.affiliation: Division of Pathological Anatomy, Papa Giovanni XXIII Hospital, Bergamo, Italy. Electronic address: lcattaneo@hpg23.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Cattaneo
authors.affiliation: Unit of Medical Oncology, Department of Oncology and Hematology, Papa Giovanni XXIII Hospital, Bergamo, Italy. Electronic address: mariomandala@tin.it.
authors.forename: Mario
authors.initials: M
authors.lastname: Mandalà
mesh_terms: D000818:Animals; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002986:Clinical Trials as Topic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D060890:B7-H1 Antigen; D061026:Programmed Cell Death 1 Receptor
keywords: Melanoma; PD-1; PD-L1