Table 1a:
Pro-tumorigenic roles of IL-17
| Species | Cancer Type | Major Findings/Mechanisms |
|---|---|---|
| Mouse | Colorectal cancer | Barrier disruption by microbial products trigger tumor-elicited inflammation, which in turn drives tumor growth (106) |
| Human | Advanced colorectal cancer | Metastatic disease was associated with elevated Th17-associated cytokines such as IL-23, IL-17F in both colonic tissue and circulation (107) |
| Mouse | Colorectal cancer | IL-17RA signals directly within transformed colonic epithelial cells (enterocytes) to promote early tumor development via an ERK, p38 MAPK and NF-κB signaling pathway(108) |
| Human | Advanced-stage colorectal cancer | Th17 cells Inhibit CD8+ T Cell Migration by downregulation of CXCR3 expression via IL-17A/STAT3 axis. (109) |
| Human | Colorectal cancer | Patients with lower IL-17 levels have increased survival of 5 years. (110) |
| Mouse | Sporadic colorectal cancer | Tumor-prone mice colonized with onco-toxin producing bacteria showed increased IL-17 in the colon and DNA damage in colonic epithelium with faster tumor onset and greater mortality.(111) |
| Mouse | Colon cancer | Damage to intestinal epithelium activates IL-17A signaling in PLET1 cells leading to aberrant wound healing favoring tumor growth. (54) |
| Mouse | Colon cancer | IL-17 targets colonic epithelial cells (CECs) to promote ETBF mediated carcinogenesis via NF-kb signaling triggering CXC chemokine to drive pro-tumoral neutrophil infiltration to distal colon. (62) |
| Mouse | Multiple myeloma | Gavaging tumor-prone mice with P. heparinolytica promotes differentiation of Th17 cells in gut and migration to bone marrow favoring multiple myeloma growth. (112) |
| Mouse | Skin cancer | IL-23 required for spontaneous skin tumors(113). Damage to skin activates IL-17A signaling in Lrig1+ stem cells leading to aberrant wound healing favoring tumor growth. (53) |
| Mouse | Liver cancer | IL-17A induced CXCL5 production by tumor cells enhance the infiltration of myeloid-derived suppressor cells thereby reducing anti-tumor immunity.(56) |
| Mouse | Lung cancer | IL-17A weakens the antitumor immunity by inhibiting apoptosis of MDSCs.(57) |
| Human | Gastric cancer | IL-17A from CD8+T cells regulates the influx of MDSCs to the tumor site via a CXCL12-CXCR4 axis to mitigate anti-tumor CD8+ T cell functions(60) |
| Human | Gastric cancer | Both IL-17A (rs2275913) and IL-17F (rs763780) polymorphisms significantly increase gastric cancer risk. (114, 115) |
| Mouse | Breast cancer | IL-17A from γδ+T cells induces the infiltration of neutrophils to suppress the CD8+ T cells function and promote metastasis.(59) |
| Mouse | Lung cancer | Commensal bacteria drive IL-17 production from γδ+ T cells to promote neutrophil infiltration and tumor cell proliferation. (61) |
| Mouse | Non-Small-Cell Lung Cancer | lL-17 drives angiogenesis by stimulating VEGF production of cancer cells via STAT3/GIV signaling. (64) |
| Human | Gall bladder cancer | IL-17 producing γδ+T cells drive VEGF production to promote blood-vessel formation (66) |
| Human | Gastric cancer | IL-17 producing neutrophils drive MMP-9 production to promote angiogenesis and tumor growth. (116) |
| Mouse | Liver Cancer, Pancreatic Cancer | IL-17 promotes chemokine signaling driven angiogenesis (68, 69) |