This project investigates Merkel cell carcinoma (MCC), an aggressive skin cancer with a high rate of metastasis and poor survival. MCC serves as an ideal model for studying virus-linked tumor immunity due to its ethiology from Merkel cell polyomavirus infection (MCPyV) or extensive UV-indued DNA damage. While MCPyV is known to influence patient outcomes, the underlying mechanisms of virus-linked immunomodulation remain poorly understood. Using multiplex proteomics, the scientists will build a spatial single-cell MCC atlas to map tumor-immune interactions and to spatially contextualize features of virus-linked immunomodulation and risk for metastatic progression. They will independently such features in external MCC cohorts for improved patient stratification and treatment selection. Prior data suggest an important role of CAF-tumor interactions for metastatic progression, which they will selectively target in new preclinical models of virus-linked MCC. This work aims to provide a foundational atlas for the spatial MCC microenvironment and identify novel therapeutic targets to reverse metastatic progression in MCC and across solid tumors - with important implications for early cancer therapies.