CTLA4 and neoplasm: Furthermore, in NK cells, the generation capacity of IFNγ and perforin were dramatically increased on day 7 after treatment, with downregulated levels of CTLA-4 and Tim-3 compared to those in the tumor-bearing controls (Figures 3F, G; Supplementary Figure S4C), suggesting the activation and improved cytotoxicity after cryo-thermal therapy.