LAUSR

MCC: Merkel cell carcinoma MCPyV: Merkel cell polyomavirus PET/CT: position emission tomography/ computed tomography PD: programmed death TVEC: talimogene laherparepvec UV: ultraviolet INTRODUCTION Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy with a propensity for locoregional recurrence and hematogenous spread. MCC typically presents in elderly patients with fair complexion as a rapidly growing, firm, fleshcolored or bluish-red cutaneous nodule on sunexposed areas, most commonly of the head and neck. It is traditionally thought to arise from Merkel cells, receptor cells located in the basal layer of the epidermis involved in the sense of light touch. Alternatively, these tumors may originate from an immature, totipotent stem cell. Merkel cell polyomavirus (MCPyV), a ubiquitous virus in the human skin microbiome, is a nonenveloped, doublestranded DNA virus directly involved in the pathogenesis of approximately 80% of MCCs. Steps involved in the development of MCPyV tumors include clonal integration into the host cell genome, mutational loss of viral replication competence, expression of 2 key oncoproteins designated small tumor antigen and large tumor antigen, retinoblastoma gene suppression by large tumor antigen, and evasion of a destructive immune response. MCPyV tumors have the highest somatic mutation burden of any characterized malignancy with ultraviolet (UV) signature mutations predominating and exhibit high levels of T-celleinfiltrating lymphocytes and programmed death (PD)-L1 expression. Thus, MCC is an attractive target for immunotherapy because MCPyV tumors contain integrated viral