. 2020 Oct 23;12(11):3099. doi: 10.3390/cancers12113099

Table 1.

Mechanistic effectors of the TGF-β pathway in the TME.

Cell Type	Factors	Cancer Type	TGF-β Function and Effect	Species	Reference
T cell	PD-1	Prostate cancer	Limit T cell activation	Human	[75,76]
	IL-1β	Mesothelioma	Limit differentiation and production of Th9 cells	Mouse	[77]
	IL-4	Mesothelioma	Limit differentiation and production of Th9 cells	Mouse	[77]
	IL-22	Colon cancer	Enhance the production of Th17 cells and cancer progression	Human	[78]
	IL-2	Colon cancer	Inhibit the function of Th17 and prevent dendritic cell (DC) antigen presentation	Mouse	[79]
	VEGFA	Melanoma	Reduce regulatory T cells (Tregs) and enhance effector T cell activation in TME	Mouse	[80]
B cell	PD-L1	Colorectal Cancer	Enhance IgA⁺ B cell production and immuno- suppression	Mouse	[81]
	LAP	Breast Cancer	Increase B cell inflation and inhibit T cell, NK cell proliferation	Mouse	[82]
	IL-15	Breast Cancer		Mouse	[82]
NK cell	NKG2D	Melanoma	Reform the phenotype of NK cells and reduce their cancer-killing effect.	Human	[83]
	NKp46	Prostate carcinoma		Human	[83]
	DNAM-1	Prostate carcinoma		Human	[83]
	NKp30	Non-small cell lung cancer		Human	[83]
	NKp80
	CD16
	ILT-2
	IL-15	Breast cancer, Prostate cancer	Reduce the metabolism and production of NK cells and decrease the amount of NK cell receptors and the cytotoxic effect of NK cells.	Mouse	[84]
	mTOR	Breast cancer, Prostate cancer		Mouse	[84]
	Smad3	Lewis lung carcinoma, Melanoma	Reduced NK cell population with limited tumour-suppressive activities, and suppress differentiation of NK cells	Mouse	[85]
	E4BP4	Lewis lung carcinoma, Melanoma		Mouse	[85]
MDSC	CD39	Non-small cell lung cancer	Limit the myeloid-derived suppressor cell (MDSC) immunosuppressive effect and enhance chemo-protective effects to tumour	Human	[86]
	CD73
	HIF-α
	IL-7	Lewis lung carcinoma	Suppress B cell responses to tumour though MDSC	Mouse	[87]
	STAT5	Lewis lung carcinoma	Suppress B cell responses to tumour though MDSC	Mouse	[87]
	iNOS	Melanoma	Enhance the release of ROS and NO in MDSCs and suppress the activity and cancer-killing effect of CD8⁺ T and NK cells	Mouse	[88]
	ARG1	Melanoma		Mouse	[88]
	Fas	HPV-associated head and neck cancer	Enhance antigen-presenting ability	Human	[89]
		HPV-associated head and neck cancer		Human	[89]
Macrophage	IFN-α	Breast cancer	Inhibit the production of pro-inflammatory cytokines and cause the M2-like differentiation	Mouse	[90]
	IL-10
	IL-12
	Snail
	IL-6	Gastric cancer	Increase M2 differentiation, lead to the proliferation and migration of tumour cells	Human	[91]
	IL-10
	STAT3
	SERPINE1	Non-small cell lung cancer	Maintain TGF-β overexpressed in TME and reduce immunosuppression	Human	[92]
	IL-17	Non-small cell lung cancer		Human	[92]
	RTK	Glioblastoma	Increase M2-polarised tumour-associated macrophage (TAM) infiltration and cancer progression	Human	[93]
	PI3K	Glioblastoma		Human	[93]
DC	IFN-α	Ovarian cancer	Alter plasmacytoid dendritic cells (pDC) functions in TME and increase recruitment, activation of Tregs	Human	[94]
	TNF-α
	IL-6
	PD-L1	Lewis lung carcinoma	Induce Treg expansion in TME	Mouse	[95]
	TNFSF18	Lewis lung carcinoma	Induce Treg expansion in TME	Mouse	[95]
	RIG-I	Hepatocellular Carcinoma	Suppresse the production and function of DCs	Human	[96]
Neutrophil	CXCL5	Hepatocellular Carcinoma	Increase neutrophil recruitment and create a pro-tumour TME	Human	[97,98]
	Kras	Hepatocellular Carcinoma	Increase neutrophil recruitment and create a pro-tumour TME	Human	[97,98]
	ALK5	Colorectal Cancer	Create a pro-tumour TME and inhibit T cell activation	Human	[99,100]
	MMP9	Colorectal Cancer	Create a pro-tumour TME and inhibit T cell activation	Human	[99,100]