Exposure to solar ultraviolet radiation (UVR) impacts various cellular, genetic, and immunologic responses governing biological and pathophysiologic events including the development of skin cancers. The mechanistic insights into UVR-induced immune tolerance against skin cancers, particularly cutaneous melanoma, have been a great challenge, given the sophisticated regulation of immune checkpoint proteins. A study led by Wang and colleagues has elucidated novel mechanisms of UVR-induced immune suppression, implicated in melanoma immune evasion and progression mediated via upregulation of PD-L1, and reduced CD8+ T-cell-mediated cytotoxicity in HMGB1/TBK1/IRF3/NF-κB-dependent manner. These findings offer new mechanistic insights into UVR-induced melanoma immune evasion and progression.See related article by Wang et al., p. 2909.