title: Radiotherapy and immune checkpoints inhibitors for advanced melanoma.
abstract: The therapeutic landscape of metastatic melanoma drastically changed after the introduction of targeted therapies and immunotherapy, in particular immune checkpoints inhibitors (ICI). In recent years, positive effects on the immune system associated to radiotherapy (RT) were discovered, and radiation has been tested in combination with ICI in both pre-clinical and clinical studies (many of them still ongoing). We here summarize the rationale and the preliminary clinical results of this approach.
  
  
  
  In the first part of this review article, redacted with narrative non-systematic methodology, we describe the clinical results of immune checkpoints blockade in melanoma as well as the biological basis for the combination of ICI with RT; in the second part, we systematically review scientific publications reporting on the clinical results of the combination of ICI and RT for advanced melanoma.
  
  
  
  The biological and mechanistic rationale behind the combination of ICI and radiation is well supported by several preclinical findings. Retrospective observational series and few prospective trials support the potential synergistic effect between radiation and ICI for metastatic melanoma.
  
  
  
  RT may potentiate anti-melanoma activity of ICI by enhancing response on both target and non-target lesions. Several prospective trials are ongoing with the aim of further exploring this combination in the clinical setting, hopefully confirming initial observations and opening a new therapeutic window for advanced melanoma patients.
authors.affiliation: Department of Oncology, Radiation Oncology, University of Torino, Italy. Electronic address: andreariccardo.filippi@unito.it.
authors.forename: Andrea Riccardo
authors.initials: AR
authors.lastname: Filippi
authors.affiliation: Department of Medical Sciences, Dermatology/Oncology, University of Torino, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Fava
authors.affiliation: Department of Oncology, Radiation Oncology, University of Torino, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Badellino
authors.affiliation: Department of Medical Sciences, Dermatology/Oncology, University of Torino, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Astrua
authors.affiliation: Department of Oncology, Radiation Oncology, University of Torino, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Ricardi
authors.affiliation: Department of Medical Sciences, Dermatology/Oncology, University of Torino, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Quaglino
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors*; D002986:Clinical Trials as Topic; D006801:Humans; D007167:Immunotherapy; D000074324:Ipilimumab; D008545:Melanoma / Q000188:drug therapy / Q000532:radiotherapy*; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors*; D011446:Prospective Studies
chemical_list: D000911:Antibodies, Monoclonal; D060908:CTLA-4 Antigen; D000074324:Ipilimumab; D061026:Programmed Cell Death 1 Receptor
keywords: Immunotherapy; Melanoma; Radiotherapy; Stereotactic radiotherapy