CTLA4 and hepatocellular carcinoma: While CD8+ T cells and NK T cells have been shown to be protective against liver tumor cells in mouse models, CD8+ TIL found within HCC in patients have been shown to be dysfunctional with low production of granzyme and perforin, low proliferation as measured by Ki-67, and upregulation of exhaustion markers such as TIM3, LAG3, PD-L1, and CTLA-4 [29, 98, 99].