Immunotherapy against programmed death-1/programmed death ligand 1 in hepatocellular carcinoma: Importance of molecular variations, cellular heterogeneity, and cancer stem cells

Table 1 Programmed death-1/programmed death ligand 1 nucleotide variations and their clinical relevance in liver disease

	Variants	Relevance	Ref.
PD-1	rs7421861	Increases cancer risk, especially in NAFLD-HCC	[127,140]
	rs2227981	Reduces cancer risk	[127]
	rs42386439	Low HBV viral load	[129]
	rs36084323	Worse disease progression in chronic HBV, low TNF-α and IFN-γ levels	[15,131,132]
	rs10204525	Disease progression in chronic HBV, high TNF-α and IFN-γ levels, longer overall survival	[131,133-135]
	rs11568821	Reduces cancer risk	[23,127,136]
PD-L1	rs4143815	Increases cancer risk	[141,143]
	rs17718883	Reduces cancer risk	[142]
	rs10815225	Increases cancer risk	[143]
	rs2297136	Increases cancer risk	[142]
	rs2890658	Not associated with cancer risk	[142]
PD-1 and PD-L1	PD-1 rs11568821 and PD-L1 rs4143815	Liver transplantation setting	[148]

PD-1: Programmed death-1; PD-L1: Programmed death ligand 1; NAFLD: Non-alcoholic fatty liver disease; HCC: Hepatocellular carcinoma; HBV: Hepatitis B virus; TNF-α: Tumor necrosis factor α; IFN-γ: Interferon-.