Merkel cell carcinoma (MCCs) is a cancer that requires additional research. It is the most deadly skin cancer. Moreover, its incidence is rising, doubling from 2000 to 2013. Until recently, there have been no effective therapies for this disease. Immunotherapies have revolutionized the treatment of MCCs. Roughly 50% of patients respond to these treatments, called PD1 inhibitors. While this is an important advance, there are critical barriers to cure. There are no biomarkers to predict who will respond to treatment. Moreover, there are no treatments for patients who fail immunotherapy. To address this critical unmet need, we have assembled a large clinical cohort of patients with MCCs across multiple institutions. We will subject them to a number of assays designed to identify what immune cells are in each sample and what they are doing. Our goal is to identify patterns that predict who responds to therapy and why or why not. The biomarkers we discover can be immediately deployed to ensure that PD1 inhibitors are only given to patients likely to respond to them. For the rest, our studies will seek to identify novel immunotherapy drug targets. If successful, we can develop new drugs that can be used against these novel targets and test them in future clinical trials. This knowledge will be critical to improve patient care and a key advance to developing a cure for this deadly disease.