Table 4.
Interleukin-17F functional studies
| Cancer | Study type | Cell lines/animal type | Main results | Authors |
|---|---|---|---|---|
| Blood | in vitro | PBMCs and CD4+ T cells | IL-17F triggers NFkB phosphorylation in T and B cells from patients with CLL, but not age-matched healthy controls. | Sherry et al. 2015 [24] |
| Breast | in vitro | MCF-7 cells | IL-17F enhances MCF-7 cell proliferation, migration and invasion via activation of the MAPK/ERK signaling pathway. | Chen et al. 2020 [81] |
| Colorectal | in vitro | HCT116 cells | IL-17F promotes cancer cell migration and invasion by inducing epithelial-mesenchymal transition | Chen et al., 2019 [15] |
| in vitro | HCT116 wild-type and IL-17F overexpressing cell clones | IL-17F plays an important role in colon cancer development through regulation of cell cycle. This could partially happen through IL-17F effects on p27 and p38. | Tong et al. 2014 [82] | |
| in vitro, in vivo | ApcMin/+ mice, CRC cell lines (DLD-1 and HT-29) | Tumor-infiltrating leukocytes produce large amounts of T helper type IL17-related cytokines, including IL-17F. Individual neutralization of IL-17F does not change the TIL-derived proproliferative effect in CRC cells. | De Simone et al., 2014 | |
| in vitro, in vivo | Cell lines (HCT116, HUVEC), BALB/c nude mice and C57BL/6 mice | IL-17F has protective role in colon cancer, possibly by inhibiting tumor angiogenesis. | Tong et al. 2012 [20] | |
| Gastric | in vitro | Gastric cancer cell line (AGS) | IL-17F, may contribute to amplification and persistence of inflammatory processes implicated in inflammation-associated cancer through activation of p65 NFkB. | Zhou et al. 2007 [83] |
| Oral | in vitro | Cell lines (HSC-3, SCC-25, SAS) | IL-17F has an antitumorigenic effect through inhibition of the vasculogenic mimicry | Almahmoudi et al. 2021 [84] |
| in vitro | Cell lines (HSC-3, SCC-25, HOKs, HUVEC, CAF) | IL-17F inhibited cell proliferation and random migration of oral cancer cells and inhibited the endothelial cell tube formation. | Almahmoudi et al. 2019 [21] | |
| Liver | in vitro, in vivo | Cell lines (293 T, SMMC-7721, ECV304), athymic nude mice | IL-17F suppresses cancer cell growth via inhibition of tumor angiogenesis. | Xie et al. 2010 [85] |
| Lung | in vitro, in vivo | Human A549 and murine LL/2 (LLC1) lung cancer cell lines, bone marrow-derived macrophages from C57BL/6 mice. Chicken chorioallantoic membrane (CAM) | IL-17A/F does not affect cancer cell viability or glycolytic metabolism in vitro. Conditioned media from IL-17A/F-stimulated macrophages promoted lung cancer cell progression through an increased migration capacity in vitro and enhanced in vivo tumor growth, proliferation and angiogenesis. | Ferreira et al. 2020 [86] |
| in vivo | CCSPcre/K-rasG12D mice | IL-17F has no effect on lung cancer development in K-ras mutated mouse model. | Chang et al. 2014 [87] | |
| Small intestine | in vivo | ApcMin/+ mice | Ablation of IL-17F significantly inhibits spontaneous intestinal tumorigenesis in the small intestine of ApcMin/+ mice. This was associated with decreased IL-1b and Cox-2 expression as well as IL-17 receptor C (IL-17RC) expression | Chae et al., 2011 [88] |
Abbrevations: CLL = chronic lymphocytic leukemia, CAF = cancer-associated fibroblasts, HOKs = human oral keratinocytes, HUVEC = human umbilical vein endothelial cells, NFkB = Nuclear Factor kappa-light-chain-enhancer of activated B cells, PBMC = peripheral blood mononuclear cell, TIL = tumor-infiltrating leukocyte