Melanoma is a type of skin cancer that often develops resistance to treatment with targeted drugs (BRAF/MEK) and checkpoint blockade immunotherapy. This resistance arises through processes in which the tumor excludes the immune system from the tumor area and changes its gene expression. The researchers suggest that androgen receptor (hormone) signaling induced by the treatment may promote the production of the B7-H3 protein, which helps the tumor hide from the immune system. In melanoma patients treated with anti-CTLA-4 immunotherapy, a positive association between the androgen receptor and B7-H3 appears after treatment, although no such association exists before treatment. Similar mechanisms have been observed in prostate cancer, where the androgen receptor directly regulates B7-H3. The researchers suggest that disrupting the androgen receptor-B7-H3 axis through modulation of the androgen receptor or agents targeting B7-H3 could represent a new therapeutic opportunity. The article outlines falsifiable mechanisms and short-term experiments to test this hypothesis and establish a basis for combination therapy in melanoma.