Our team based in Seattle conducted a comprehensive review including evolving trends in the management of Merkel cell carcinoma (MCC). This summary covers key decision points, including recommended work-up during initial diagnosis, treatment options for MCC when it’s in one place or has spread, management of recurrent MCC, and new treatments that are showing promise with fewer side effects and good results. This review gives valuable information on how to handle MCC overall and emphasizes new methods that are effective and less toxic on patients.
Merkel cell carcinoma (MCC) is a virally associated cancer characterized by its aggressive behavior and strong immunogenicity. Both viral infection and malignant transformation induce expression of MHC class I chain-related protein (MIC) A and B, which signal stress to cells of the immune system via Natural Killer group 2D (NKG2D) resulting in elimination of target cells. However, despite transformation and the continued presence of virally-encoded proteins, MICs are only expressed in a minority of MCC tumors in situ and are completely absent on MCC cell lines in vitro. This lack of MIC expression was due to epigenetic silencing via MIC promoter hypo-acetylation; indeed, MIC expression was re-induced by pharmacological inhibition of histone deacetylases (HDACs) both in vitro and in vivo. This re-induction of MICs rendered MCC cells more sensitive to immune-mediated lysis. Thus, epigenetic silencing of MICs is an important immune escape mechanism of MCCs.