Rationale for immune-based therapies in Merkel polyomavirus-positive and -negative Merkel cell carcinomas

Immunotherapy. 2016 Jul;8(8):907-21. doi: 10.2217/imt-2016-0009.

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.

Keywords: Merkel cell carcinoma; Merkel cell polyomavirus; PD-1; PD-L1; exhaustion; immune evasion; immune therapy.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigens, Viral, Tumor / immunology
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Merkel Cell / immunology
  • Carcinoma, Merkel Cell / therapy*
  • Humans
  • Immunotherapy / methods*
  • Polyomavirus / immunology*
  • Polyomavirus Infections / immunology*
  • Polyomavirus Infections / therapy
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Skin Neoplasms / immunology
  • Skin Neoplasms / therapy*
  • Tumor Escape
  • Tumor Virus Infections / immunology
  • Tumor Virus Infections / therapy*

Substances

  • Antigens, Viral, Tumor
  • Antineoplastic Agents
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor