Non-Genetic Biomarkers in Merkel Cell Carcinoma: Prognostic Implications and Predictive Utility for Response to Anti-PD-(L)1 Immune Checkpoint Inhibitors

Merkel cell carcinoma (MCC) is a skin cancer that arises due to either Merkel cell polyomavirus infection (MCPyV) or ultraviolet (UV) radiation exposure, presenting primarily in the head and neck region of fair-skinned males. The recent success of PD-(L)1 immune checkpoint inhibitors (ICIs) in locally advanced/metastatic MCC, with an objective response rate (ORR) around 50% and improved survival, as a first-line treatment has moved ICIs to the forefront of therapy for MCC and generated interest in identifying biomarkers to predict clinical response. The MCC tumour microenvironment (TME) contains various components of the adaptive and innate immune system. These components can contribute to tumour immune escape through immunosuppression by preventing entrance of other immune cells or by aiding in the cytotoxic clearance of tumour cells. We aim to combine information from studies of baseline and on-treatment monitoring of the TME to help predict the success of ICIs in MCC. This review enhances the understanding of how CD8 T cells, γδ T cells and macrophages may impact predictions of response rates to ICIs in MCC patients. These immune cells are non-genetic biomarkers that can also be used to determine prognosis in MCC treatment.