Interleukin 17, a T-cell-derived cytokine, promotes tumorigenicity of human cervical tumors in nude mice.
ABSTRACT Interleukin (IL) 17 is a proinflammatory cytokine secreted mainly by activated human memory CD4 T cells that induces IL-6, IL-8, and nitric oxide. Because IL-6 and IL-8 have been implicated in the pathogenesis of cervical cancer, we investigated the action of IL-17 on human cervical tumor cell lines in vitro and in vivo. We showed that in vitro, IL-17 increases IL-6 and IL-8 secretion by cervical carcinoma cell lines at both protein and mRNA levels. No direct effect of IL-17 on in vitro proliferation of cervical tumor cell lines could be demonstrated. However, two cervical cell lines transfected with a cDNA encoding IL-17 exhibited a significant increase in tumor size as compared to the parent tumor when transplanted in nude mice. This enhanced tumor growth elicited by IL-17 was associated with increased expression of IL-6 and macrophage recruitment at the tumor site. A potential role of IL-17 in modulation of the human cervical tumor phenotype was also supported by its expression on the cervical tumor in patients with CD4 infiltration. IL-17 therefore behaves like a T-cell-specific cytokine with paradoxical tumor-promoting activity. This may partially explain previous reports concerning the deleterious effect of CD4 T cells in cancer.
SourceAvailable from: PubMed Central[Show abstract] [Hide abstract]
ABSTRACT: Interleukin-17 (IL-17) is prevalent in tumor tissue and suppresses effective anti-tumor immune responses. However, the source of the increased tumor-infiltrating IL-17 and its contribution to tumor progression in human gastric cancer remain poorly understood. In this study, we enrolled 112 gastric cancer patients, immunofluorescence was used to evaluate the colocalization of CD3, CD4, CD56, CD20, CD68, and mast cell tryptase (MCT) with IL-17. Immunohistochemistry was used to evaluate the distribution of microvessel density (CD34), CD66b+, CD68+, and FoxP3+ cells in different microanatomical areas. Prognostic value was determined by Kaplan-Meier analysis and a Cox regression model. The results showed that mast cells, but not T cells or macrophages, were the predominant cell type producing IL-17 in gastric cancer. Significant positive correlations were detected between densities of mast cell-derived IL-17 and microvessels, neutrophils, and regulatory T cells (Tregs). Futhermore, we found that the majority of vascular endothelial cells expressing Interleukin-17 receptor (IL-17R). Kaplan-Meier analysis revealed that increasing intratumor infiltrated mast cells and IL-17+ cells, as well as MCT+ IL-17+ cells, were significantly associated with worse overall survival. These findings indicated that mast cells were the major source of IL-17 in gastric cancer, and intratumor IL-17 infiltration may have promoted tumor progression by enhancing angiogenesis in the tumor microenvironment through the axis of IL-17/IL-17R. IL-17-positive mast cells showed a prognostic factor in gastric cancer, indicating that immunotherapy targeting mast cells might be an effective strategy to control intratumor IL-17 infiltration, and consequently reverse immunosuppression in the tumor microenvironment, facilitating cancer immunotherapy.PLoS ONE 09/2014; 9(9):e106834. DOI:10.1371/journal.pone.0106834 · 3.53 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Interleukin-17 (IL-17A) expression is increased in prostate cancer. This study investigated the expression of IL-17A receptor C (IL-17RC) in prostatic intraepithelial neoplasia (PIN) lesions and the effects of IL-17A on prostatic epithelial cells in in-vitro studies.
[Show abstract] [Hide abstract]
ABSTRACT: Psoriasis is a chronic inflammatory skin disorder resulting from a complex network of cytokines and chemokines produced by various immune cell types and tissue cells. Emerging evidence suggests a central role of IL-17 and IL-23/T17 axis in the pathogenesis of psoriasis, giving a rationale for using IL-17-blocking agents as therapeutics. Three agents targeting IL-17 signaling are being studied in Phase III clinical trials: secukinumab and ixekizumab (IL-17 neutralizing agents), and brodalumab (IL-17 receptor antagonist). Preliminary results are highly promising for all anti-IL17 agents, creating fair expectations on this class of agents as the new effective therapeutic approach for the treatment of psoriasis.Actas Dermo-Sifiliográficas 10/2014; 105S1:9-20. DOI:10.1016/S0001-7310(14)70014-6