The development of immunotherapy has recently modified the anti-tumor therapeutic arsenal ; particularly, immune checkpoint inhibitors have led to a significant increase in overall survival. The current challenge is now to select good responder patients by identifying early biomarkers to propose therapeutic combinations that potentiate the efficacy of the therapy. Here we report the case of a 60-year-old man with superficial melanoma treated with high-dose hypo fractionated radiotherapy (H-SRT) combined with a single dose of anti-PD1 immunotherapy (Nivolumab) for a metastatic lymph node recurrence due to cancer progression. In this study, we present the results obtained regarding the activation of the Th1 immune response after H-SRT treatment followed by anti PD-1 therapeutic protocol. These results were correlated with clinical data to identify potential immunological biomarkers of treatment efficacy. This exceptional case report shows that a combination of H-SRT with a single dose of anti-PD1 immunotherapy may allow a better activation of the immune response in favor of a complete clinical response.