Table 4.

Soluble immune molecules showing a statistically significant over-expression in responder patients: characteristics and function.

Soluble Molecules	Class of Molecules	Cell Source	Ligands	Main Function	Type of Action	References
IL13	Cytokyne	T CD4 Cells CD8 cells NK B-cells Monocytes Eosinophils Mast cells	IL13Rα1 IL13Rα2	-involved in Th2 immune responses -potentiate expression of adhesion molecules on endothelial cells -activation of magrophages and production of TGFb -key regulator of extracellular matrix	proinflammatory	[47]
IL17A	Cytokine	Lymphocytes TCD4 Th17	IL17Rα	-induces IL6 and chemokines production -promotes recruitment of MDSCs into the tumour bed -neutrophil recruitment, anti-microbial molecule and acute phase protein production	proinflammatory	[48]
TNF alpha	Cytokine	Macrophages NK T cells	TNFR1 TNFR2	-pro-inflammatory activity -fever -Acute phase response -stimulates cell proliferation and survival	Immune-activation/ pro-inflammatory	[49]
IL4	Cytokine	T cells Mast cells	IL4-Rα	-activation of Th2 immune response -Cell growth/activation -B-cell growth factors and stimulate B-cell differentiation.	Pro-inflammatory	[50,51]
INF alpha	Cytokine	DC Macrophages NK cells Macrophages Endothelial cells Fibroblasts	INFαR1/2	-NK activation -Cells B proliferation -Possible suppression of Treg cells -Antiviral activity -Enhances MHC expression	Pro-inflammatory immune-activation	[52]
INF gamma	Cytokine	Lymphocytes T (th1) CD8 and NK	INFγR1/2	-activation of macrophages -activation of Th1 responses -potential antigen presentation to T lymphocytes -induces apoptosis of tumour cells and reduces VEGF -increases expression of IDO	immunoactivating/ possible immunosuppressive activity)	[53]

DC dendritic cells, IL interleukin, IFN interferon, TNF tumor necrosis factor, NK natural killer, MDSC myeloid derived suppressor cell, TGF trasforming growth factor, VEGF vascular endothelial growth factor, IDO Indoleamine 2,3-dioxygenase.