Expression and location of IL-17A, E, F and their receptors in colorectal adenocarcinoma: Comparison with benign intestinal disease

Abstract

The research aimed to investigate secretion, expression and location of IL-17 relative ligands, IL-17 relative receptors, infiltrating inflammatory cells and parenchymal structural cells in colorectal cancer (CRC) compared with ulcerative colitis (UC) and benign hyperplastic polyp. 29 human intestinal tissues with CRC, 17 with UC and 7 with polyp were stained using immunohistochemistry to evaluate immunoreactivity for IL-17 family relative ligands including IL-17A, E, F and their respective relative receptors such as IL-17RA, IL-17RB and IL-17RC. At the same time the infiltration of inflammatory cells including lymphocytes, phagocytes, mast cells and neutrophils and parenchymal structural cell changes involving vascular endothelial cells and CD90 fibroblast cells were also evaluated using the same methods The immunoreactivity or positive inflammatory cells of all the sections were analyzed using professional image analysis software to determine statistical significance. The immunoreactivity for IL-17A, IL-17RA, IL-17E, IL-17RB and IL-17F showed significant decrease in CRC tissue when compared to UC (p = 0.00001. respectively). The reduction of above IL-17 relative ligands and receptors was accompanied by an obvious decrease in the number of infiltrating neutrophils and mast cells in CRC (p = 0.00001 and p = 0.007, respectively) but accompanied by a marked increase of CD31 blood vessels (p = 0.001). The immunoreactivity of IL-17A, IL-17RA, IL-17E, IL-17RB and IL-17F and the numbers of infiltrating neutrophils and mast cells showed significant decrease in CRC tissues when compared to those in polyp (p < 0.05). In contrast, the immunoreactivity of IL-17RC and the numbers of CD3 1ymphocytes were elevated in CRC when compared with those in polyp (p = 0.0001, p = 0.007, respectively). In CRC tissues, positive correlations between IL-17A, IL-17RA with CD68 macrophages were observed respectively (r = 0.621, p = 0.0001; r = 0.75, p = 0.0001). IL-17 cytokine family including ligands and their corresponding receptors were secreted and expressed by infiltrating inflammatory cells. Not only infiltrating lymphocytes but also increased blood endothelial cells were relative significantly to genesis and progression of CRC.

Modeling of the immune response in the pathogenesis of solid tumors and its prognostic significance

“…The level of expression of proinflammatory IL-17A and its receptor IL-17RA has been found to be significantly higher in UC and in benign gut polyps than in CRC. The levels of other ligands from the IL-17 family (E/F) and IL-17RB receptors, along with neutrophil and mast cell infiltration, were significantly reduced in cancer compared to benign lesions, unlike the IL17RC ligand, which together with CD3 + cell infiltration was more highly expressed in CRC than in polyps [217]. The levels of other cytokines may also change.…”

Increase expression of IL-17A, IL6, STAT3, TGF-β and VEGF in Bladder Cancer: potential biomarkers?

“…Thus, any potential biomarkers for predicting the prognosis and malignancy of the disease are worth to be investigated. Our previous studies proved that elevated expression of IL-17A was observed in tissues derived from bladder cancer, prostate cancer and rectal carcinoma [5,23,24] suggesting that this cytokine may promote occurrence and development of malignant diseases.…”

The Role of Inflammatory Cytokines in the Pathogenesis of Colorectal Carcinoma—Recent Findings and Review

“…Nevertheless, the release of IL-17A by CEA-specific T cells after CRC surgery does not seem responsible for the poorer survival of those patients [ 146 ]. On the contrary, IL-17F expression seems to be usually downregulated in CRC cells [ 147 , 148 ]. Omrane et al reported that the wildtype IL17F gene was associated with longer OS in CRC patients [ 149 ].…”