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

Table 3 Association between programmed death-1 expression and cancer stem cell markers

Malignancy	Stemness/CSC markers	Method	Relevance	Ref.
HCC	CD133+ interaction with lymphatic endothelial cells	Co-culture	Upregulates PD-L1	[196]
HCC	CK-19, SALL-4	IHC	Positively associated with PD-L1	[194]
HCC	EpCAM	IHC	Negatively associated with PD-L1	[194]
Breast cancer	CD44hiCD24lo	Flow cytometry	High PD-L1 expression	[182]
Breast cancer	EpCAM+CD44hi CD24lo	Flow cytometry	High PD-L1 expression	[184]
Breast cancer	EpCAM+CD90hi	Flow cytometry	High PD-L1 expression	[184]
Breast cancer	EpCAM+CD44hiCD24lo	Flow cytometry, IF	High PD-L1 expression; nuclear PD-L1	[185]
Breast cancer	Stemness score	mRNA from TCGA	Significant correlation to PD-L1	[185]
Breast cancer	ALDH+, CD44hi	Flow cytometry	High PD-L1 expression	[183]
Colorectal cancer	CD44hiCD133hi	Flow cytometry	High PD-L1 expression	[182]
Colorectal cancer	CD133+CD44+	Flow cytometry	High PD-L1 expression	[189]
Ovarian cancer	ALDH	qRT-PCR, IF	High PD-L1 expression	[188]
HNSCC	CD44+	Flow cytometry, qRT-PCR, RNA in situ hybridization	High PD-L1 expression	[191]
Lung adenocarcinoma	CD44	mRNA in TIMER datasets	Positively associated with PD-L1	[186]
NSCLC	ALDH	mRNA from TCGA, IHC	Negatively associated with PD-L1	[192]
Cholangiocarcinoma	ALDH	Sorting of PD-L1 cells	High ALDH+ in PD-L1lo	[193]
Pancreatic cancer	CD44+CD133+	IF	Positively associated with PD-L1	[190]

PD-1: Programmed death-1; PD-L1: Programmed death ligand 1; IHC: Immunohistochemistry; TCGA: The Cancer Genome Atlas; qRT-PCR: Quantitative real-time polymerase chain reaction; HNSCC: Head and neck squamous cell carcinoma; NSCLC: Non-small cell lung carcinoma; HCC: Hepatocellular carcinoma.