title: Combinatorial immunotherapy with checkpoint blockers solves the problem of metastatic melanoma-An exclamation sign with a question mark.
abstract: Results from recent clinical trials demonstrate that a combinatorial immunotherapeutic regimen based on 2 distinct checkpoint blockers, namely, the CTLA4-targeting agent ipilimumab and the PD-1-specific molecule nivolumab, causes objective responses in a majority of subjects with advanced melanoma. These findings revolutionize the treatment of a neoplasm that was considered incurable until recently. Nonetheless, announcing the defeat of melanoma appears premature. Indeed, a sizeable fraction of patients does not respond to ipilimumab plus nivolumab, and the long-term efficacy of this immunotherapeutic regimen has not yet been investigated. Moreover, many patients experience severe side effects, calling for the development of strategies that uncouple the efficacy of ipilimumab plus nivolumab from their toxicity.
authors.affiliation: INSERM ; U1138; Paris, France ; Université Paris Descartes/Paris V; Sorbonne Paris Cité ; Paris, France ; Université Pierre et Marie Curie/Paris VI ; Paris, France ; Equipe 11 labellisée Ligue contre le Cancer; Center de Recherche des Cordeliers ; Paris, France ; Metabolomics and Cell Biology Platforms; Gustave Roussy Comprehensive Cancer Institute ; Villejuif, France ; Pôle de Biologie, Hôpital Européen Georges Pompidou; AP-HP ; Paris, France.
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
authors.affiliation: INSERM ; U1138; Paris, France ; Université Paris Descartes/Paris V; Sorbonne Paris Cité ; Paris, France ; Université Pierre et Marie Curie/Paris VI ; Paris, France ; Equipe 11 labellisée Ligue contre le Cancer; Center de Recherche des Cordeliers ; Paris, France ; Gustave Roussy Comprehensive Cancer Institute ; Villejuif, France.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Galluzzi
keywords: CTLA4; Opdivo™; PD-1; PD-L1; Yervoy™; pembrolizumab