CTLA4 and melanoma: Although it was shown that prolonged exposure to IFN-Is did not induce therapeutic resistance in B16-F10 melanoma to anti-CTLA-4 and RT [75], another study using different types of tumor models (sarcoma, CRC, and breast tumor) demonstrated that sustained IFN-I signaling induced secondary resistance to anti-PD-1 that was developed after four rounds of anti-PD-1 treatments.