HAVCR2 and hepatocellular carcinoma: Tim3 was originally found to suppress the effector Th1 responses in murine model of multiple sclerosis.71 In chronic viral infection, Tim3 expression is highly persistent and is associated with the inflammatory regulation of T cells.72 In cancer, Tim3+ TILs in lung cancer patients exhibited significant defects in cytokine production and T-cell proliferation.3,73 Furthermore, co-expressed Tim3+ PD-1+ TILs were demonstrated to represent a deeply exhausted T-cell population, with a strong association to tumor progression such as in prostate, colorectal, and hepatocellular carcinoma.74,75