Most melanomas were reported to highly express PD-L1.561 Actually, PD-L1 is expressed in tumor cells and myeloid cells in the tumor environment mainly mediated by constitutive activation of oncogenic signal pathways in tumor cells and IFNγ signaling.499,562 The expression of PD-L2 is highly upregulated in certain B cell lymphoma.501 Given that PD-1 binds to both PD-L1 and PD-L2, and PD-1 interacts with either CD80 or PD-L1, the antibodies targeting PD-1 or PD-L1 may lead to different antitumor effects and toxicities,563 which has been supported by relevant clinical trials of anti-PD-L1. This evidence concerns the gene CD274 and melanoma.