Specific CD8+ T cell response immunotherapy for hepatocellular carcinoma and viral hepatitis

Table 1 Clinical trials of immune checkpoint inhibitors in patients with chronic hepatitis and hepatocellular carcinoma

NCT	Status	Disease	Agent	Result	Ref.
01008358	Completed	HCC and CHC	Tremelimumab	TTP: 6.48 m	[30]
01853618	Recruiting	HCC	Tremelimumab	TTP: 7.4 m	[111]
00703469	Completed	CHC	Nivolumab	15% significant reduction of viral load	[31]
02658019	Not yet recruiting	HCC	Pembrolizumab	NA	[112]
01658878	Recruiting	HCC	Nivolumab	NA	[113]
			Ipilimumab

Tremelimumab and ipilimumab are humanized monoclonal antibodies against CTLA-4; Nivolumab and pembrolizumab are humanized monoclonal antibodies against PD-1. HCC: Hepatocellular carcinoma; NA: Not available; NCT: Clinical trial number at clinicaltrials.gov; TTP: Time to progression.

Table 2 Overexpressed negative pathways in liver diseases

Disease	Overexpressed NR	Ligand for the overexpressed NR
HCC	CTLA-4[29], PD-1[12]	PD-L1[26], CD48[135]
CHB	CTLA-4[28], PD-1[25], LAG-3[117], Tim-3[129]	PD-L1[136]
CHC	CTLA-4[27], PD-1[24,105,106], LAG-3[116], 2B4[13,122], Tim-3[128]	PD-L1[44]

Overexpression of negative receptors on specific CD8⁺ T cells in different malignancies and overexpression of their cognate ligands in the liver tissue. CHB: Chronic hepatitis B; CHC: Chronic hepatitis C; HCC: Hepatocellular carcinoma; NR: Negative receptor.