Immune evasion mechanisms and immune checkpoint inhibition in advanced merkel cell carcinoma

Oncoimmunology. 2017 Aug 31;6(10):e1338237. doi: 10.1080/2162402X.2017.1338237. eCollection 2017.


Merkel cell carcinoma (MCC) is a rare skin cancer caused by Merkel cell polyomavirus (MCPyV) infection and/or ultraviolet radiation-induced somatic mutations. The presence of tumor-infiltrating lymphocytes is evidence that an active immune response to MCPyV and tumor-associated neoantigens occurs in some patients. However, inhibitory immune molecules, including programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1), within the MCC tumor microenvironment aid in tumor evasion of T-cell-mediated clearance. Unlike chemotherapy, treatment with anti-PD-L1 (avelumab) or anti-PD-1 (pembrolizumab) antibodies leads to durable responses in MCC, in both virus-positive and virus-negative tumors. As many tumors are established through the evasion of infiltrating immune-cell clearance, the lessons learned in MCC may be broadly relevant to many cancers.

Keywords: Avelumab; Merkel cell carcinoma; PD-1; PD-L1; checkpoint inhibition; immune evasion; pembrolizumab.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't