The Role of the Immune Response in Merkel Cell Carcinoma

Abstract

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer. The Merkel cell polyomavirus (MCPyV) is implicated in its pathogenesis. Immune mechanisms are also implicated. Patients who are immunosuppressed have an increased risk. There is evidence that high intratumoral T-cell counts and immune transcripts are associated with favorable survival. Spontaneous regressions implicate immune effector mechanisms. Immunogenicity is also supported by observation of autoimmune paraneoplastic syndromes. Case reports suggest that immune modulation, including reduction of immune suppression, can result in tumor regression. The relationships between MCPyV infection, the immune response, and clinical outcome, however, remain poorly understood. Circulating antibodies against MCPyV antigens are present in most individuals. MCPyV-reactive T cells have been detected in both MCC patients and control subjects. High intratumoral T-cell counts are also associated with favorable survival in MCPyV-negative MCC. That the immune system plays a central role in preventing and controlling MCC is supported by several observations. MCCs often develop, however, despite the presence of humoral and cellular immune responses. A better understanding on how MCPyV and MCC evade the immune response will be necessary to develop effective immunotherapies.

Merkel cell polyomavirus infection and Merkel cell carcinoma

“…The role of MCPyV in MCC development, along with the fact that immune-suppressed individuals are more likely to develop this cancer, indicate that the host immune response plays a key role in MCC tumorigenesis [54]. Additional evidence such as complete spontaneous tumor regression and tumor reactive T cells all support the role of the immune system in preventing and controlling MCC [55]. Furthermore, MCC patients with robust immune response generally have better prognoses, and high intratumoral CD8+ and CD4+ lymphocyte infiltration predicts better survival [56–58].…”

Spontaneous regression in an ulcerated CK7 positive Merkel cell carcinoma

“…Individuals with Merkel cell polyoma virus positivity are thought to have a more favorable outcome, possibly due to the immune response triggered by the virus. [10] Our patient showed complete regression of lesions within 1 month of biopsy. The presence of Merkel cell polyoma virus was not assessed in our case.…”

Spontaneous regression and recurrence of stage III Merkel cell carcinoma

“…On the other hand, it is suggested that some form of immune modulation may result in (complete) tumour regression. This theory is supported by the various histopathological observations in patients with complete spontaneous regression of MCC, which show signs of chronic inflammation with humoral and cellular immune responses leading to replacement of the original tumour cells 1 16. Since biopsy preceded the complete regression in all of the written case reports, it is plausible to conclude that this probably was the triggering mechanism.…”