Together with the synergistic effect of GZMA and PRF1 in patient survival, we provide evidence that CYT-high skin melanoma patients who are to receive CTLA-4 and/or PD-1 checkpoint blockade therapy, have a markedly higher immunophenoscore and are consequently, expected to have a clinical benefit, compared to CYT-low patients. Here, GZMA is linked to cutaneous melanoma.