Therefore, cSCCs, HNSCCs, and melanomas mostly composed of epithelial Ecad+ cancer cells may respond better to anti-PD-1/PD-L1 therapy, while those composed of epithelial Ecad+ and mesenchymal Vim+ cancer cells, and that do not respond to anti-PD-1/PD-L1 therapy, may be treated with anti-CTLA-4 or anti-TIGIT therapies, or even with combined ICB therapies, to improve their clinical outcomes. The gene discussed is CTLA4; the disease is melanoma.