IL-17 can promote tumor growth through an IL-6–Stat3 signaling pathway

By Lin Wang, T. Yi, M. Kortylewski, D. Pardoll, D. Zeng, Hua Yu. Journal of Experimental Medicine, 2009

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Although the Th17 subset and its signature cytokine, interleukin (IL)-17A (IL-17), are implicated in certain autoimmune diseases, their role in cancer remains to be further explored. IL-17 has been shown to be elevated in several types of cancer, but how it might contribute to tumor growth is still unclear. We show that growth of B16 melanoma and MB49 bladder carcinoma is reduced in IL-17−/− mice but drastically accelerated in IFN-γ−/− mice, contributed to by elevated intratumoral IL-17, indicating a role of IL-17 in promoting tumor growth. Adoptive transfer studies and analysis of the tumor microenvironment suggest that CD4+ T cells are the predominant source of IL-17. Enhancement of tumor growth by IL-17 involves direct effects on tumor cells and tumor-associated stromal cells, which bear IL-17 receptors. IL-17 induces IL-6 production, which in turn activates oncogenic signal transducer and activator of transcription (Stat) 3, up-regulating prosurvival and proangiogenic genes. The Th17 response can thus promote tumor growth, in part via an IL-6–Stat3 pathway.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/f8a035f7690191dde271b59d3299e39eb76dea85

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Citations in the corpus

Cancer immunotherapy comes of age (2011, positive): “Lastly, the importance of tumour-promoting inflammatory pathways, such as STAT3 and NF-kB signalling, and cytokines including IL-6, IL-17, IL-23 and tumour-necrosis factor-a (TNF-a) has been demonstrate”
Immunity, Inflammation, and Cancer (2010, neutral): “TAMs can be also ‘‘programmed’’ by tumor-infiltrating T cells, particularly Th17 cells (Wang et al., 2009) and Th2 cells (DeNardo et al.”
The JAK/STAT signaling pathway: from bench to clinic (2021, background): “In addition, cyclooxygenase-2, IL-17, IL-21, and IL-23 encoded by NF-κB can activate STAT3 in various ways.(200,203,204) IL4-mediated STAT6 activation plays a crucial role in inflammatory gene inhibition, partly because STAT6 acts as an antagonist of NFκB upon the binding of the E-selectin gene prom”
Dangerous liaisons: STAT3 and NF-κB collaboration and crosstalk in cancer (2009, background): “Several mechanisms, which are not mutually exclusive, were proposed, including a role for STAT3 in the immunosuppressive action of IL-10 and inhibition of DC maturation as well as its effects on MDSC differentiation and recruitment (5,97), STAT3- dependent production of angiogenic factors (79) as we”
Microbiota organization is a distinct feature of proximal colorectal cancers (2014, methodology): “Can biofilms modify epithelial biology before initiation of transformation? To evaluate this conjecture, we conducted analyses of colonic epithelial cell biologic changes relevant to carcinogenesis, including barrier permeability (using the cell– cell adhesion molecule epithelial cadherin (E-cadheri”
Inflammation and Cancer: Triggers, Mechanisms and Consequences (2019, background): “For example, cancer cells instruct fibroblasts to acquire differentiation states which are tumor-promoting and immunosuppressive (Alexander and Cukierman, 2016) but activation of fibroblasts also can be driven by cytokines, such as IL-6 or IL-17, released by immune cells (Majumder et al., 2019; Wang”
FAP Promotes Immunosuppression by Cancer-Associated Fibroblasts in the Tumor Microenvironment via STAT3-CCL2 Signaling. (2016, result): “The role of STAT3 in cancer has been largely focused on tumor cells and myeloid cells (18,32), however, we showed robust STAT3 activation in CAFs, which is consistent with several studies (29,33), and identify FAP as a persistent activator of fibroblastic STAT3, which in turn mediates inflammatory p”