UVB Effect on Melanoma Patient Response to Immunotherapy

Ultraviolet B (UVB) radiation is a primary driver of cutaneous melanoma and a major contributor to its high tumor mutational burden. Classically, this mutational load generates neo-antigens that generally correlate with a favorable response to immune checkpoint inhibitors. However, melanomas arising in chronically sun-damaged skin frequently exhibit therapeutic resistance. This review proposes to uncouple the beneficial effect of UVB-induced neo-antigens from the broader consequences of UVB exposure that may also promote treatment resistance. Identifying these specific UV-induced factors provides a framework to better predict immunotherapy failure in high tumor mutational burden patients and highlights novel therapeutic targets.