T-Cell Mediated Immunity in Merkel Cell Carcinoma

SIMPLE SUMMARY: Efforts have been directed toward exploring the pathophysiology underlying virus-positive and virus-negative Merkel cell carcinoma. An increasing amount of research has underlined the role of T-cells in the initiation, progression, and clearance of this rare skin cancer. An updated summary of recent research exploring T-cell-mediated immunity in Merkel cell carcinoma informs future research directions as well as targets for immunotherapy. ABSTRACT: Merkel cell carcinoma (MCC) is a rare and frequently lethal skin cancer with neuroendocrine characteristics. MCC can originate from either the presence of MCC polyomavirus (MCPyV) DNA or chronic ultraviolet (UV) exposure that can cause DNA mutations. MCC is predominant in sun-exposed regions of the body and can metastasize to regional lymph nodes, liver, lungs, bone, and brain. Older, light-skinned individuals with a history of significant sun exposure are at the highest risk. Previous studies have shown that tumors containing a high number of tumor-infiltrating T-cells have favorable survival, even in the absence of MCPyV DNA, suggesting that MCPyV infection enhances T-cell infiltration. However, other factors may also play a role in the host antitumor response. Herein, we review the impact of tumor infiltrating lymphocytes (TILs), mainly the CD4(+), CD8(+), and regulatory T-cell (Tregs) responses on the course of MCC, including their role in initiating MCPyV-specific immune responses. Furthermore, potential research avenues related to T-cell biology in MCC, as well as relevant immunotherapies are discussed.