Although previous studies have reported the synergistic efficacy of combinational anti-PD-1 plus anti-TIM-3 treatment in xenograft and carcinogen-induced tumour models31, we provide here the first evidence showing the efficacy of TIM-3 blockade following anti-PD-1 therapy failure in genetically engineered mouse model in the context of adaptive resistance, which reproduces a more clinically relevant situation as demonstrated by our two case vignettes1, 32. Here, HAVCR2 is linked to neoplasm.