STAT3 activation

Figures & data

Table 1. Main STAT3 modulators and their effects in immune cells

Cell type	pSTAT3 modulators	Effects
CD4+ T cell	IL-27	↑ proliferation
Th17	IL-6, IL-21, IL-23	↑ RORγt and RORα expression and ↑ cell differentiation ↑ IL-21, IL-23R and IL-17
	IL-6 (in combination with TGF-β)	↑ CD39 and CD73 expression and ↑ adenosine production
Treg	IL-2	↑ Foxp3 expression (associated with pSTAT5) and ↑ inhibitory functions
	IL-6, IL-27	↓ Foxp3 expression (with an inhibition of pSTAT5 binding) and inhibition of differentiation
		↑ IL-6, TGF-β (with Foxp3 cooperation)
Macrophage	IL-6	Inhibition of differentiation
		Inhibition of Ag presentation to CTL, ↑ IL-23 and ↓ IL-12 production Inhibition of LPS-mediated cytokine production (e.g., RANTES and IL-12)
	Tumor cell supernatants	↑ IL-10, βFGF and VEGF-A production and ↑ angiogenesis
DC		Inhibition of Ag presentation to CTL and ↓ TLR induced IL-12 and TNF-α production
	Tumor cell supernatants, IL-6 and exosomes	↓ differentiation (with an IL-6 amplification loop)
MDSC	exosomes	↑ immunosuppressive functions (with an IL-6 amplification loop)
	Tumor cell supernatant	↑ production of VEGF and βFGF and ↑ angiogenesis
		↑ expression of NOX2, ↑ production of ROS and ↑ immunosuppressive functions

Figure 1. Effects of STAT3 presence (STAT3^+/+) or absence (STAT3^−/−) within immune cells. STAT3 activation leads to the activation of Treg and Th17 cells, the differentiation of M2 macrophages, the accumulation of MDSCs and the absence of functional DCs. STAT3 deletion or inhibition leads to the inhibition of Treg and Th17 cells, the differentiation of MDSCs into DCs, a good antigen presentation to CTLs by macrophages and DCs leading to an anti-tumor immune response.