We also developed in vivo AR models using murine syngeneic BrafV600MUT melanoma with high mutational burden (YUMM1.7ER or YER), which responds to anti-PD-1 + anti-CTLA-4 therapy in a CD8+ T cell-dependent manner.52 We treated YER P tumors with combined ICIs twice a week, selecting for tumors that relapsed after initial tumor regression lasting 25–35 days (AR1, AR2) or >110 days (AR3). This evidence concerns the gene CTLA4 and melanoma.