title: Immunotherapy in melanoma: Recent advances and future directions.
abstract: Malignant melanoma contributes the majority of skin cancer related deaths and shows an increasing incidence in the past years. Despite all efforts of early diagnosis, metastatic melanoma still has a poor prognosis and remains a challenge for treating physicians. In recent years, improved knowledge of the pathophysiology and a better understanding of the role of the immune system in tumour control have led to the development and approval of several immunotherapies. Monoclonal antibodies against different immune checkpoints have been revolutionizing the treatment of metastatic and unresectable melanoma. Ipilimumab, a monoclonal antibody against the cytotoxic T-lymphocyte antigen 4 (CTLA-4) as well as nivolumab and pembrolizumab which target the programmed cell death protein 1 (PD-1) have been shown to prolong overall survival in patients with advanced melanoma. The latter substances seem to have an increased response rate and more tolerable safety profile compared to ipilimumab. The combination of a CTLA-4 and a PD-1 inhibitor seems to be superior to the monotherapies, especially in patients with PD-L1 negative tumours. Checkpoint inhibitors are currently being tested in the adjuvant setting with initial data for ipilimumab suggesting efficacy in this context. Talimogene laherparepvec (TVEC) is the first oncolytic virus approved in the therapy of metastatic melanoma offering a treatment option especially for patients with limited disease. In this review, data on these recently developed and approved immunotherapies are presented. However, further studies are necessary to determine the optimal duration, sequencing and combinations of immunotherapies to further improve the outcome of patients with advanced melanoma.
authors: Department of Dermatology, Venereology and Allergology, University Hospital, University of Duisburg-Essen, Essen, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany.
authors: C
authors: C
authors: Franklin
authors: Department of Dermatology, Venereology and Allergology, University Hospital, University of Duisburg-Essen, Essen, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany.
authors: E
authors: E
authors: Livingstone
authors: Department of Dermatology, Venereology and Allergology, University Hospital, University of Duisburg-Essen, Essen, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany.
authors: A
authors: A
authors: Roesch
authors: Department of Dermatology, Venereology and Allergology, University Hospital, University of Duisburg-Essen, Essen, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany. Electronic address: Bastian.Schilling@uk-essen.de.
authors: B
authors: B
authors: Schilling
authors: Department of Dermatology, Venereology and Allergology, University Hospital, University of Duisburg-Essen, Essen, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany. Electronic address: Dirk.Schadendorf@uk-essen.de.
authors: D
authors: D
authors: Schadendorf
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors; D005544:Forecasting; D006801:Humans; D007167:Immunotherapy / Q000379:methods / Q000639:trends*; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D050130:Oncolytic Virotherapy; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors; D012878:Skin Neoplasms / Q000276:immunology / Q000628:therapy*
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D060908:CTLA-4 Antigen; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
keywords: Immune-checkpoint blockade; Immunotherapy; Melanoma; Oncolytic virus