CTLA4 and hepatocellular carcinoma: However, CD8+ TILs separated from human HCC tissues are functionally exhausted as determined by upregulated expression of PD-1, Tim-3 [29], CTLA-4, and lymphocyte activation gene 3 (LAG-3) [31] compared with those from human CHB tissues [37], tumor-free liver tissues [29, 34], and peripheral blood [34].