VSIR and hepatocellular carcinoma: We found that almost all the major T cell exhaustion markers were expressed significantly higher in CYT-high HCC, which include PD-1, PD-L1, CTLA4, indoleamine 2,3-dioxygenase 1 (IDO1), IDO2, lymphocyte-activation gene 3 (LAG3), T cell immunoglobulin and mucin domain 3 (TIM3), programmed death-ligand 2 (PD-L2), T cell immunoreceptor with Ig and ITIM domains (TIGIT), adenosine A2a receptor (ADORA2A), and V-domain Ig suppressor of T cell activation (VISTA) (Figure 4a).