Table 2.

Relationship among HHLA2 expression, PD-L1 expression, TIL density, and other factors in different tumours.

Human cancer type	Results	Ref.
Cervical adenocarcinoma	HHLA2 expression was positively related to PD-L1.	[78]
Clear cell renal cell carcinoma	HHLA2 expression did not overlap with PD-L1 expression.	[10]
	HHLA2 expression was positively and significantly associated with PD-L1 and PD-L2 at the mRNA level in whole tumour samples but individual cells were not examined	[76]
	HHLA2 expression was positively related to CD8.	[74]
	The positive rates of HHLA2 were more widespread than PD- L1. HHLA2/PD- L1 co-expression was related to a high density of CD8+ and CD4+ TILs.	[75]
Glioma	HHLA2 was negatively related to specific genes, including IL-10, TGF-β, VEGF, DDL4, and other immune checkpoint molecules, including PD-L1, LAG3, and B7H3.	[71]
Hepatocellular carcinoma	HHLA2 expression was related to the density of TILs but not to PD-L1 levels.	[66]
	The expression levels of HHLA2 and PD-L1 were negatively correlated.	[67]
Intrahepatic cholangiocarcinoma	HHLA2 expression was more frequent than PD-L1 expression. HHLA2 and PD-L1 co-expression were infrequent, and 50 % of PD-L1-negative samples had elevated HHLA2 expression. HHLA2 high expression was related to fewer CD3+ TILs and CD8+ TILs as well as a higher CD4+ Foxp3+/CD8+ TIL ratio.	[9]
Ovarian cancer	High HHLA2 expression was positively related to the density CD8+ TILs.	[60]
Osteosarcoma	TILs were present in 75 % of tumour specimens.	[62]
Lung cancer	Increased CD8 expression was related to more prolonged disease-free survival.	[36]
	HHLA2 limited co-expression with PD-L1, and HHLA2 was commonly expressed in PD-L1 negative tumours.	[79]
Colorectal carcinoma	The HHLA2 expression level was significantly associated with the invasion depth and CD8+T-cell infiltration status.	[73]