BioProject

Merkel cell polyomavirus (MCPyV) is the causative agent for most Merkel cell carcinomas (MCC). More...

Merkel cell polyomavirus (MCPyV) is the causative agent for most Merkel cell carcinomas (MCC). This highly aggressive skin cancer shows rapid progression, with metastasis being a significant challenge for patient therapy. Virus positive MCCs show low mutation rates and tumor cell proliferation is dependent on viral oncoproteins, small-T (sT), and large-T (LT) antigen. While the role of sT and LT in early events of tumorigenesis has been extensively studied, their role in tumor progression has been scarcely addressed. Here, we investigate possible mechanisms of how MCPyV oncoproteins, e.g., sT, contribute to metastasis. We show that sT specifically affects selectin ligand binding and processing by altering the presentation of multiple MCC surface molecules, thereby influencing initial metastasis events and tumor cell immune recognition.Furthermore, we demonstrate that sT regulates the surface antigen CD47, which inhibits phagocytosis by macrophages. By applying either sT or CD47 targeted siRNAs or applying a therapeutic anti-CD47 antibody, we show that immune recognition of MCC cells can be restored. Thus, CD47 is a promising new therapeutic target on Merkel cell carcinoma cells. Blocking the CD47-SIRPα interaction effectively promotes phagocytosis of MCC cells and might be a promising combinatorial immunotherapy approach together with PD-1/PD-L1 axis in MCC treatment. Less...