In a recent study, CD155 was reported to act as an immune checkpoint ligand for tumor and tumor-associated myeloid cells, thus representing a potential novel ICI target.33 Furthermore, it was reported that elevated expression of CD155 in human metastatic melanoma is associated with decreased sensitivity to anti-PD-1 immunotherapy.34 It, however, remains to be established whether a combination of PD-1 blockade and downstream activation of CD155-CD226 could create costimulatory cytotoxic signaling in CD8+ T cells, and whether this might exert a synergistic therapeutic effect. This evidence concerns the gene PDCD1 and metastatic melanoma.