Ricerc@Sapienza

Merkel cell carcinoma (MCC) is a very aggressive neuroendocrine cancer. The overall survival (OS) in MCC patients who have localized disease is about 50%. But those with distant metastasis have an abysmal OS of only about 10-14%. A neuroendocrine carcinoma, MCC presents as firm reddish nodules on the skin of elderly patients. In a small proportion of patients, the skin lesions are absent but the tumor is localized in the lymph node. The risk of MCC is higher in immunosuppressed individuals. Significantly, Most MCCs are infected with recently identified virus, Merkel cell Polyoma virus (MCPyV). It is not clear whether the MCPyV infection which underlies the MCC development is the cause or consequence of immunosuppression. Previously, we have shown that viruses can alter cellular miRNAs to alter immune checkpoints like PD-L1 in lymphoma. In the present proposal, we would like to examine an Italian cohort of MCC for the presence of MCPyV, expression of immune checkpoints (IC) and IC targeting miRNAs. Using both MCPyV positive and negative MCC cell lines, first we will establish miRnome of these cell lines to understand how the presence of MCPyV affects cellular miRNAs. Subsequently, we will analyze expression of PD-L1, PD-L2 and other IC proteins in MCC which are infected in vitro. We will identify virally encoded proteins which influence IC expression. To better understand, molecular mechanisms behind IC alteration, we will investigate IC targeting miRNAs, like miR-34a, miR-24, miR-200c. Towards identification of novel biomarkers for MCC, we propose to investigate deregulated cellular miRNAs in sera from MCC patients and healthy controls.