title: Rationale for immune-based therapies in Merkel polyomavirus-positive and -negative Merkel cell carcinomas.
abstract: Merkel cell carcinoma (MCC) is a rare but often deadly skin cancer that is typically caused by the Merkel cell polyomavirus (MCPyV). Polyomavirus T-antigen oncoproteins are persistently expressed in virus-positive MCCs (˜80% of cases), while remarkably high numbers of tumor-associated neoantigens are detected in virus-negative MCCs, suggesting that both MCC subsets may be immunogenic. Here we review mechanisms by which these immunogenic tumors evade multiple levels of host immunity. Additionally, we summarize the exciting potential of diverse immune-based approaches to treat MCC. In particular, agents blocking the PD-1 axis have yielded strikingly high response rates in MCC as compared with other solid tumors, highlighting the potential for immune-mediated treatment of this disease.
authors.affiliation: Department of Medicine (Pathology & Dermatology), University of Washington, USA.
authors.forename: Natalie
authors.initials: N
authors.lastname: Vandeven
authors.affiliation: Department of Medicine (Pathology & Dermatology), University of Washington, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Nghiem
mesh_terms: D000818:Animals; D000957:Antigens, Viral, Tumor / Q000276:immunology; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015266:Carcinoma, Merkel Cell / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D011120:Polyomavirus / Q000276:immunology*; D027601:Polyomavirus Infections / Q000276:immunology* / Q000628:therapy; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors; D012878:Skin Neoplasms / Q000276:immunology / Q000628:therapy*; D019139:Tumor Escape; D014412:Tumor Virus Infections / Q000276:immunology / Q000628:therapy*
chemical_list: D000957:Antigens, Viral, Tumor; D000970:Antineoplastic Agents; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
keywords: Merkel cell carcinoma; Merkel cell polyomavirus; PD-1; PD-L1; exhaustion; immune evasion; immune therapy