Merkel cell carcinoma (MCC) is an aggressive, polyomavirus-associated skin cancer. Robust cellular immune responses are associated with excellent outcomes in MCC patients, but are typically absent. We determined the prevalence and reversibility of class I MHC (MHC-I) downregulation in MCC, a potentially reversible immune evasion mechanism. Cell surface MHC-I expression was assessed on 5 MCC cell lines using flow cytometry as well as immunohistochemically on tissue microarrays representing 114 patients. Three additional patients were included who had received intralesional interferon treatment and had evaluable before and after specimens. mRNA expression analysis of antigen presentation pathway genes from 35 MCC tumors was used to examine mechanisms of down-regulation. 84% of MCCs (n=114) demonstrated reduced MHC-I expression as compared to surrounding tissues and 51% had poor or undetectable expression. Expression of MHC-I was lower in polyomavirus-positive MCCs as compared to virus-negative MCCs (p<0.01). The MHC-I downregulation mechanism was multifactorial and did not depend solely on HLA gene expression. Treatment of MCC cell lines with ionizing radiation, etoposide, or interferon resulted in MHC-I upregulation, with interferons strongly upregulating MHC expression in vitro and in 3 of 3 patients treated with intralesional interferon. MCC tumors may be amenable to immunotherapy, but downregulation of MHC-I is frequently present in these tumors, particularly those that are polyomavirus-positive. This downregulation is reversible with any of several clinically available treatments that may thus promote the effectiveness of immune stimulating therapies for MCC.
- Received January 10, 2014.
- Revision received June 24, 2014.
- Accepted July 21, 2014.
- Copyright © 2014, American Association for Cancer Research.