Tartour E, Fossiez F, Joyeux I, Galinha A, Gey A, Claret E et al.. Interleukin 17, a T-cell-derived cytokine, promotes tumorigenicity of human cervical tumors in nude mice. Cancer Res 59: 3698-3704

Unité d'Immunologie Clinique, INSERM U 225 and Université Pierre et Marie Curie, Paris, France.
Cancer Research (Impact Factor: 9.33). 09/1999; 59(15):3698-704.
Source: PubMed


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.

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    • "Clinically , neutrophil recruitment has also recently been associated with higher MVD and therefore a more aggressive disease in gastric cancer [91]. IL-17-induced IL-8 release was shown with human cervical cancer [62] and in human glioblastoma cell lines [61]; interestingly the latter study also demonstrated a dose-dependent increase in Ií µí¼…B-í µí»¼ mRNA expression, whose product protein is required for NF-í µí¼…B expression. This transcription factor is well characterized to produce numerous proinflammatory cytokines including IL- 6 and IL-8 [103] "
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    ABSTRACT: With 7.6 million deaths globally, cancer according to the World Health Organisation is still one of the leading causes of death worldwide. Interleukin 17 (IL-17) is a cytokine produced by Th17 cells, a T helper cell subset developed from an activated CD4+ T-cell. Whilst the importance of IL-17 in human autoimmune disease, inflammation, and pathogen defence reactions has already been established, its potential role in cancer progression still needs to be updated. Interestingly studies have demonstrated that IL-17 plays an intricate role in the pathophysiology of cancer, from tumorigenesis, proliferation, angiogenesis, and metastasis, to adapting the tumour in its ability to confer upon itself both immune, and chemotherapy resistance. This review will look into IL-17 and summarise the current information and data on its role in the pathophysiology of cancer as well as its potential application in the overall management of the disease.
    Mediators of Inflammation 07/2014; 2014(4):623759. DOI:10.1155/2014/623759 · 3.24 Impact Factor
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    • "Recently, it was reported that TH-17 cell number and IL-17 levels are increased in cervical cancers compared to normal cervical tissues [14]. It has previously been shown that IL-17 promotes growth of human xenograft cervical tumors through recruitment of macrophages to the tumor site [15]. We have previously demonstrated that IL-17, as a chemoattractant, can directly recruit monocytes/macrophages into the tumor microenvironment [6]. "
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    ABSTRACT: Purpose Interleukin-17 (IL-17) is a proinflammatory cytokine that plays important roles in inflammation, autoimmunity, and cancer. The purpose of this study was to determine if IL-17 indirectly regulates macrophage differentiation through up-regulation of cyclooxygenase-2 (COX-2) expression in the cancer cell lines. Materials and Methods Human cervical cancer HeLa, human lung cancer A549, and mouse prostate cancer Myc-CaP/CR cell lines were treated with recombinant IL-17; Western blot analysis, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction analysis were utilized to examine the cellular responses. Results IL-17 up-regulated expression of COX-2 mRNA and protein in HeLa, A549, and Myc- CaP/CR cell lines. IL-17’s effects were mediated through nuclear factor-κB and ERK1/2 signaling pathways as the inhibitors of these pathways could inhibit IL-17- induced COX-2 expression. The conditional medium obtained from the cancer cells contained prostaglandin E2, the levels of which were increased by IL-17 treatment. When treated with the conditional medium, particularly with the IL-17-induced conditional medium, mouse RAW264.7 macrophages and human THP-1 monocytes expressed higher levels of IL-10 (a marker of M2 macrophages) than inducible nitric oxide synthase or tumor necrosis factor α (markers of M1 macrophages). In contrast, when RAW264.7 and THP-1 cells were treated directly with IL-17, expression of these marker genes was not markedly changed. Conclusion The results of this study suggest that IL-17 indirectly promotes M2 macrophage differentiation through stimulation of the COX-2/PGE2 pathway in the cancer cells, thus IL-17 plays an indirect role in regulating the tumor immune microenvironment.
    Cancer Research and Treatment 07/2014; 46(3):297-306. DOI:10.4143/crt.2014.46.3.297 · 3.32 Impact Factor
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    • "Th17 cells were previously detected in both murine and human solid tumors [29]–[32], but their contribution to tumor pathogenesis has remained unclear. Some studies in murine systems have shown that IL-17 could impair immune surveillance, and it promoted carcinogenesis and neovascularization in many solid tumors [30], [32]. In contrast, other studies have reported the anti-tumor effect of IL-17 and Th17 cells in mice [33]–[34]. "
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    ABSTRACT: Background and Aims An immune imbalance in the cytokine profile exerts a profound influence on the progression of hepatitis B virus (HBV) infections and hepatocellular carcinoma (HCC). The present study evaluated the immune status of T helper (Th) 17 and Th1 cells in patients with HBV-related and non-HBV-related HCC. Methods We randomly enrolled 150 patients with HCC. Blood samples and tissue samples were obtained. The distributions and phenotypic features of Th17 and Th1 cells were determined by flow cytometry and/or immunohistochemistry. Results Compared to corresponding non-tumor regions, the levels of Th17 and Th1 cells were significantly increased in tumors of patients with HCC (P<0.001). The intratumoral densities of IL-17-producing cells and IFN-γ-producing cells were associated with overall survival (OS, P = 0.001) and disease-free survival (DFS, P = 0.001) of patients with HCC. The ratio of Th17 to Th1 in HBV-related HCC was higher than in non-HBV-related HCC. A multivariate Cox analysis revealed that the Th17 to Th1 ratio was an independent prognostic factor for OS (HR = 2.651, P = 0.007) and DFS (HR = 2.456, P = 0.002). Conclusions HBV infections can lead to an imbalance in immune status in patients with HCC. An elevated Th17 to Th1 ratio may promote tumor progression. The Th17 to Th1 ratio could serve as a potential prognostic marker for scoring the severity of HCC.
    PLoS ONE 05/2014; 9(5):e96080. DOI:10.1371/journal.pone.0096080 · 3.23 Impact Factor
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