A role for IL-27p28 as an antagonist of gp130-mediated signaling

Stumhofer, Jason S.; Tait, Elia D.; Quinn, William J.; Hosken, Nancy; Spudy, Björn; Goenka, Radhika; Fielding, Ceri Alan; O'Hara, Aisling; Chen, Yi; Jones, Michael L.; Saris, Christiaan J. M.; Rose-John, Stefan; Daniel, J.; Jones, Simon A.; Elloso, M. Merle; Grötzinger, Joachim; Cancro, Michael P.; Levin, Steven D.; Hunter, Christopher A.

doi:10.1038/ni.1957

Cited by 170 publications

(217 citation statements)

References 61 publications

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“…IL-27p28 itself is recently reported to be an antagonist of gp130-mediated signaling (42). Recombinant murine IL-27 (rmIL-27) or recombinant murine IL-27p28 (rmIL-27p28) was administrated directly into tumors of Itgax-p28 f/f mice to formally verify the antitumor activity of IL-27.…”

Section: Il-27 In Vivo Reconstitution Restored Tumor Resistance In P2mentioning

confidence: 99%

Critical Role of Dendritic Cell–Derived IL-27 in Antitumor Immunity through Regulating the Recruitment and Activation of NK and NKT Cells

Wei

Xia

Sun

et al. 2013

The Journal of Immunology

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Critical roles of IL-27 in autoimmune diseases and infections have been reported; however, the contribution of endogenous IL-27 to tumor progression remains elusive. In this study, by using IL-27p28 conditional knockout mice, we demonstrate that IL-27 is critical in protective immune response against methyl-cholanthrene–induced fibrosarcoma and transplanted B16 melanoma, and dendritic cells (DCs) are the primary source. DC-derived IL-27 is required for shaping tumor microenvironment by inducing CXCL-10 expression in myeloid-derived suppressor cells and regulating IL-12 production from DCs, which lead to the recruitment and activation of NK and NKT cells resulting in immunological control of tumors. Indeed, reconstitution of IL-27 or CXCL-10 in tumor site significantly inhibits tumor growth and restores the number and activation of NK and NKT cells. In summary, our study identifies a previous unknown critical role of DC-derived IL-27 in NK and NKT cell–dependent antitumor immunity through shaping tumor microenvironment, and sheds light on developing novel therapeutic approaches based on IL-27.

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Section: Il-27 In Vivo Reconstitution Restored Tumor Resistance In P2mentioning

confidence: 99%

Critical Role of Dendritic Cell–Derived IL-27 in Antitumor Immunity through Regulating the Recruitment and Activation of NK and NKT Cells

Wei

Xia

Sun

et al. 2013

The Journal of Immunology

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“…IL-30 has so far been shown to act as a natural antagonist of gp130-mediated signaling in response to IL-6 and IL-27 and thus resulting in anti-inflammatory effects (6), whereas more recently it has been reported to signal via IL-6 a-receptor (IL-6R) by recruiting a gp130 homodimer (15).…”

Section: Introductionmentioning

confidence: 99%

Interleukin-30 Expression in Prostate Cancer and Its Draining Lymph Nodes Correlates with Advanced Grade and Stage

Meo

Airoldi

Sorrentino

et al. 2014

Clinical Cancer Research

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Purpose: The interleukin (IL)-27 cytokine subunit p28, also called IL-30, has been recognized as a novel immunoregulatory mediator endowed with its own functions. These are currently the subject of discussion in immunology, but completely unexplored in cancer biology. We set out to investigate the role of IL-30 in prostate carcinogenesis and its effects on human prostate cancer (hPCa) cells.Experimental Design: IL-30 expression, as visualized by immunohistochemistry and real-time reverse transcriptase PCR on prostate and draining lymph nodes from 125 patients with prostate cancer, was correlated with clinicopathologic data. IL-30 regulation of hPCa cell viability and expression of selected gene clusters was tested by flow cytometry and PCR array.Results: IL-30, absent in normal prostatic epithelia, was expressed by cancerous epithelia with Gleason ! 7% of 21.3% of prostate cancer stage I to III and 40.9% of prostate cancer stage IV. IL-30 expression by tumor infiltrating leukocytes (T-ILK) was higher in stage IV that in stage I to III prostate cancer (P ¼ 0.0006) or in control tissue (P ¼ 0.0011). IL-30 expression in prostate draining lymph nodes (LN)-ILK was higher in stage IV than in stage I to III prostate cancer (P ¼ 0.0031) or in control nodes (P ¼ 0.0023). The main IL-30 sources were identified as CD68 þ macrophages, CD33 þ

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“…4), IL30 can bind Epstein-Barr virus-induced 3 (EBI3) to form IL27, which has revealed antitumoral effects in several models (5,6), but it also acts as a self-standing cytokine with its own functional properties (7). It has been shown to bind to, but not signal via, the receptor (R) chain gp130, thereby antagonizing signaling via the receptors for IL6 and IL27, resulting in antiinflammatory effects (8), but also to signal via IL6R by recruiting a gp130 homodimer, behaving similarly to IL6 and IL11 and thus endowed with proinflammatory potential (9). The immunologic functions of IL30 are thus complex and currently under active investigation, whereas its role in cancer biology is mostly unknown.…”

Section: Introductionmentioning

confidence: 99%

Interleukin-30 Promotes Breast Cancer Growth and Progression

et al. 2016

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The inflammatory tissue microenvironment that promotes the development of breast cancer is not fully understood. Here we report a role for elevated IL30 in supporting the breast cancer cell viability and invasive migration. IL30 was absent in normal mammary ducts, ductules, and acini of histologically normal breast and scanty in the few stromal infiltrating leukocytes. In contrast, IL30 was expressed frequently in breast cancer specimens where it was associated with triple-negative and HER2 þ molecular subtypes. In stromal leukocytes found in primary tumors or tumor-draining lymph nodes, which included mainly CD14 þ monocytes, CD68 þ macrophages, and

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A role for IL-27p28 as an antagonist of gp130-mediated signaling

Cited by 170 publications

References 61 publications

Critical Role of Dendritic Cell–Derived IL-27 in Antitumor Immunity through Regulating the Recruitment and Activation of NK and NKT Cells

Critical Role of Dendritic Cell–Derived IL-27 in Antitumor Immunity through Regulating the Recruitment and Activation of NK and NKT Cells

Interleukin-30 Expression in Prostate Cancer and Its Draining Lymph Nodes Correlates with Advanced Grade and Stage

Interleukin-30 Promotes Breast Cancer Growth and Progression

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