Table 1.

Extracellular factors involved in the regulation of PD-L1.

Factor	Experiment Type	Cell Lines	Effects on PD-L1	Studied Effect
Check point
Soluble PD-1 [149]	Co-culture and Docetaxel treatment	DU145 and Jurkat	Act.	↑ Docetaxel resistance
Soluble factors produced by stromal cells
AREG [121]	Conditioned medium	DU145, PC3, LNCaP	↑	↑ Proliferation, migration and invasion
IL-6 [97]	Conditioned medium	Dentritic cells	↑	//
Soluble factors produced by adipocytes
Not identified [136]	Co-culture with conditioned medium	C4-2 and NK; CWR22Rv1 and NK	↑	↓ NK cytotoxicity
Soluble factors produced by macrophages
Not identified [134]	Co-culture with conditioned medium	C4-2 and NK; CWR22Rv1 and NK	↑	↓ NK cytotoxicity
Cytokine/Chemokine and Complement factors
IL-27 [151]	Treatment	PC3	↑	//
IFN-γ [10,13,94,103,112,119,128,139,152]	Treatment	PC3	↑	//
IFN-γ [94]	Treatment	Vcap CWR22Rv1, E006AA	↑	//
IFN-γ [126]	Treatment	TRAMP-C2	↑	//
IFN-γ [13]	Treatment	LASCPC, NCI-H660	↑	//
IFN-γ [126]	Treatment	DU145	=	//
IFN-γ [13,94,128]	Treatment	LNCaP	=	//
IFN-γ [94]	Treatment	LAPC-4	=	//
IFN-γ [13]	Treatment	BPH1, C4-2, CWRR-1	=	//
IFN-γ [10,94,112,119,152]	Treatment	DU145	↑	//
IFN-γ [112]	Treatment	TRAMP-C2 Ras	↑	//
IFN-γ [106]	Treatment	TRAMP-C1, MyC-CaP	↑	//
Ab anti-IL-6 [134,135,136]	Treatment	C4-2, CWR22Rv1	↓	//
IL-6 [135]	Treatment	C4-2, CWR22Rv1	↑	//
IL-17 [145]	Treatment	LNCaP	↑	//
TNF-α [145]	Treatment	LNCaP	↑	//
Chemerin [105]	Treatment of co-culture	DU145 and T	↓	↑ T cytotoxicity
C5a [18]	Treatment	PC3, C4-2	↑	//
Hypoxia
[65]	Co-culture	C4-2 and NK; CWR22Rv1 and NK	↑	↓ NK cytotoxicity

Act. Activation; ↑ Upregulation; ↓ Downregulation; = No alteration; // No effect was investigated.