Role of T_H17 cytokines in the control of colorectal cancer

Figures & data

Figure 1. Overview of the role of T_H17 cytokines and downstream signaling pathways in colorectal carcinoma. Abbreviations: IL, interleukin; STAT3, signal transducer and activator of transcription 3; PGE₂, prostaglandin E₂; VEGF, vascular endothelial growth factor; TNFα, tumor necrosis factor α

Table 1. Role of T_H17 cytokines in mouse models of colorectal carcinoma

Cytokine	Model	Effects	Ref.
IL-17A	Subcutaneous inoculation of MC38 cells	IL-17A ectopically overexpressed in MC38 cells enhances the growth of cancer cells and tumor vascularity	35
IL-17A	Subcutaneous inoculation of MC38 cells	Increased growth and enhanced lung metastasis of MC38 cells following implantation in IL-17A-deficient mice	36
IL-17A*	Subcutaneous inoculation of MC38 cells	No difference in tumor growth between wild-type and IL-17A-deficient mice	37
IL-17A	Apc^min/+ mice	IL-17A-deficient mice show reduced tumor formation and decreased production of pro-inflammatory cytokines (e.g., IL-6, IL-23), as compared with wild-type mice	38
IL-17A	Apc^min/+ mice infected with ETBF	Blockade of IL-17A inhibits ETBF-induced colitis and tumor formation	39
IL-17A	AOM/DSS-induced colitis-associated CRC	IL-17A-deficient mice express reduced levels of IL-6, STAT3, TNFα and IFNγ and develop milder colitis as well as fewer and smaller tumors than wild-type mice	40
IL-17A, IL-17F	CPC-APC mice	IL-17RA-deficient mice show upregulation of IL-17A and IL-17F and reduced tumor growth as compared with wild-type mice	42
IL-17F	HCT-116 cell xenografts in immunodeficient mice	IL-17F-overexpressing CRC cells proliferate less than control CRC cells	30
IL-17F	AOM/DSS-induced colitis-associated CRC	IL-17F-deficient mice develop more tumors than wild-type mice and this effect is associated with increased tumor angiogenesis	30
IL-21	AOM/DSS-induced colitis-associated CRC	IL-21-null mice have reduced colonic inflammation and limited tumor burden as compared with wild-type mice. These effects are associated with reduced CD4^+ T-cell infiltration, increased production of IL-6 and IL-17A, as well as enhanced STAT3 activation	29
IL-21	AOM/DSS-induced colitis-associated CRC	IL-21-deficient mice show decreased IL-17A expression, increased IFNγ content, low epithelial cell proliferation and prominent epithelial cell death in intestinal tumors as compared with wild-type mice	48
IL-22	HCT-116 cell xenografts in immunodeficient mice	IL-22 promotes the growth of HCT-116-derived xenografts and this effect is associated with STAT3 activation	31
IL-22	AOM/DSS-induced colitis-associated CRC	IL-22BP-deficient mice develop more and larger tumors than wild-type mice	55
IL-22	AOM/DSS-induced colitis-associated CRC	IL-22-null mice develop an elevated tumor load compared with wild-type mice	55
IL-22	Apc^min/+ mice	IL-22BP-null Apc^min/+ mice show an exacerbation in intestinal tumorigenesis compared with Apc^min/+ mice	55
IL-22	Apc^min/+ mice	IL-22-deficient Apc^min/+ mice exhibit a reduced tumor burden compared with Apc^min/+ mice	55
IL-22	Colitis-associated CRC induced by infection with Helicobacter hepaticus and AOM in 129SvEv.RAG-deficient mice	Antibody-mediated neutralization of IL-22 selectively decreases STAT3 activation in epithelial cells and reduces tumor burden	56

White background = pro-tumorigenic effect; gray background = anti-tumorigenic effect; * = no effect. Abbreviations: AOM, azoxymethane; DSS, dextran sodium sulfate; CPC-APC mice, Apc^F/wt mice that harbor a Cdx2-Cre transgene; CRC, colorectal carcinoma; ETBF, enterotoxigenic Bacteroides fragilis; IFNγ, interferon γ; IL, interleukin; STAT3, signal transducer and activator of transcription 3; TNFα, tumor necrosis factor α