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

Abstract

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.

• Authors: Dirk Schadendorf, Paul Nghiem, Shailender Bhatia, Axel Hauschild, Philippe Saiag, Lisa Mahnke, Subramanian Hariharan, Howard L Kaufman
• Journal: Oncoimmunology (Oncoimmunology) 2017 Vol. 6 Issue 10 Pg. e1338237 ISSN: 2162-4011 [Print] United States
• PMID: 29123950 (Publication Type: Journal Article, Review, Research Support, Non-U.S. Gov't)