Clinical and molecular characteristics associated with response to therapeutic PD-1/PD-L1 inhibition in advanced Merkel cell carcinoma

BACKGROUND: Based on its viral-associated or UV-associated carcinogenesis, Merkel cell carcinoma (MCC) is a highly immunogenic skin cancer. Thus, clinically evident MCC occurs either in immuno-compromised patients or based on tumor-intrinsic immune escape mechanisms. This notion may explain that although advanced MCC can be effectively restrained by treatment with PD-1/PD-L1 immune checkpoint inhibitors (ICIs), a considerable percentage of patients does not benefit from ICI therapy. Biomarkers predicting ICI treatment response are currently not available. METHODS: The present multicenter retrospective study investigated clinical and molecular characteristics in 114 patients with unresectable MCC at baseline before treatment with ICI for their association with therapy response (best overall response, BOR). In a subset of 21 patients, pretreatment tumor tissue was analyzed for activation, differentiation and spatial distribution of tumor infiltrating lymphocytes (TIL). RESULTS: ) in close proximity to tumor cells in patients with a favorable therapy response. CONCLUSIONS: among TIL, as baseline parameters associated with a favorable response to PD-1/PD-L1 ICI therapy of advanced MCC. These factors should be considered when making treatment decisions in MCC patients.