Table 1.

Studies reporting the effect of immune checkpoint inhibitor blockades on CD8+ T cell function in HCV infection.

Reference	Immune Checkpoint Blocked	Stage of HCV Infection	Number of Subjects	Character of the Study	Results
Golden Mason et al. [68]	PD-ligand 1 (PD-L1) PD-ligand 2 (PD-L2)	chronic	7	In vitro	↑ proliferation of HCV-specific CD8+ T cells ↑ IFN-ϒ and IL-2 secretion by HCV-specific CD8+T cells
Golden Mason et al. [69]	Tim-3	chronic	4	In vitro	↑ proliferation of HCV-specific CD8+ T cells ↑ IFN-ϒ secretion by HCV-specific CD8+ T cells ↓ IL-10 secretion by HCV-specific CD8+ T cells
Penna et al. [18]	PD-L1	chronic	8	In vitro	↑ expansion of HCV-specific CD8+ T cells ↑ frequency of both IFN-γ– and IL-2–secreting HCV-specific CD8+ T cells
Urbani et al. [70]	PD-L1	acute	8	In vitro	↑ expansion and IFN-γ and IL-2 production but not the cytolytic activity of HCV-specific CD8+ T cells.
McMahan et al. [71]	Tim-3, PD-L1, PD-L2	acute/chronic	6/4	In vitro	↑ proliferation of HCV-specific CD8+ T cells achieved by either PD-1 or Tim-3 blockade ↑ cytotoxicity of HCV-specific CD8+ T cells (increased expression of CD107a, killing of hepatocytes cell line expressing cognate HCV epitopes) achieved exclusively by Tim-3 blockade
Fuller et al. [72]	PD-1	chronic	3 chimpanzees	In vivo	↓ HCV viral load in one of three treated animals ↑ frequencies and IFN-ϒ production of intrahepatic HCV-specific CD4+ and CD8+ T cells in the same animal
Gardiner et al. [73]	PD-1	chronic	54	In vivo	↓ viral load in five patients (two patients achieved undetectable HCV RNA)
Sangro et al. [74]	CTLA-4	chronic	20	In vivo	↓ viral load sustained in most patients for 3 months follow-up; transient complete viral response in 15% of patients during follow-up ↑ HCV-specific T cell response (IFN-ϒ production)

↑ —increase; ↓ —decrease.