The role of IL-37 in cancer

Ding, Vivi A.; Zhu, Ziwen; Xiao, Hualiang; Wakefield, Mark R.; Bai, Qian; Fang, Yujiang

doi:10.1007/s12032-016-0782-4

Cited by 36 publications

(20 citation statements)

References 41 publications

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“…It has been well established that inflammation is closely related to carcinogenesis . As an anti‐inflammatory cytokine, many studies have suggested the antitumor role of IL‐37 in various tumor types, which have been reviewed previously . Here, we will describe the most recent progress for the role of IL‐37 in fibrosarcoma, breast cancer, lung cancer, ovarian cancer, renal cell carcinoma (RCC), oral squamous cell carcinoma (OSCC), cervical cancer, colon cancer, multiple myeloma (MM), prostate cancer, and HCC.…”

Section: Il‐37 In Tumormentioning

confidence: 96%

“…44,45 As an anti-inflammatory cytokine, many studies have suggested the antitumor role of IL-37 in various tumor types, which have been reviewed previously. 46,47 Here, we will describe the most recent progress for the role of IL-37 in fibrosarcoma, breast cancer, lung cancer, ovarian cancer, renal cell carcinoma (RCC), oral squamous cell carcinoma (OSCC), cervical cancer, colon cancer, multiple myeloma (MM), prostate cancer, and HCC. We will also discuss in details about the recent studies on the immune regulatory function of IL-37 in antitumor immune response, as well as its role in angiogenesis.…”

Section: Il-37 In Tumormentioning

confidence: 99%

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IL‐37: An anti‐inflammatory cytokine with antitumor functions

Liu

2018

Cancer Reports

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Background IL‐37 is a newly identified IL‐1 family cytokine. Unlike other members in IL‐1 family, IL‐37 has been demonstrated to be an anti‐inflammatory cytokine in many inflammatory and autoimmune diseases. IL‐37 is regarded as a dual‐function cytokine as both the extracellular and intracellular IL‐37 are biologically functional. Extracellular IL‐37 can bind to IL‐18Rα and IL‐1R8 to form a triple complex, regulating the downstream STAT3 and PTEN signaling. Intracellular IL‐37 can interact with Smad3, translocate into nucleus, and regulate downstream target gene expressions. Recently, the role of IL‐37 in tumor development has been extensively studied. Recent findings IL‐37 has been found to play an antitumor role in various types of tumors, such as non‐small cell lung cancer, hepatocellular carcinoma, and renal cell carcinoma. Many mechanism studies have been carried out to elaborate the possible effects of IL‐37 on tumor growth, immune responses, and tumor angiogenesis. More importantly, the function of IL‐37 may be dependent on its concentration and receptor expression. It can form dimers at high concentrations to be inactivated, thus inhibiting its anti‐inflammatory function. We focused on the role of IL‐37 in various tumor types and provided the hypothesis regarding the underlying mechanisms. Conclusion IL‐37 may affect tumor development through multiple mechanisms: (1) IL‐37 directly influences tumor cell viability; (2) IL‐37 regulates the immune response to promote the antitumor immunity; and (3) IL‐37 suppresses tumor angiogenesis in the tumor microenvironment. Future studies are warranted to further investigate the mechanisms of these multifaceted functions of IL‐37 in animal models and cancer patients.

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Section: Il‐37 In Tumormentioning

confidence: 96%

Section: Il-37 In Tumormentioning

confidence: 99%

IL‐37: An anti‐inflammatory cytokine with antitumor functions

Liu

2018

Cancer Reports

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“…Conversely, anti‐inflammatory IL‐37 might suppress tumorigenesis by inhibiting protumorigenic inflammation. Indeed, the protective role of IL‐37 in cancer has been reported when IL‐37 was transfected into cancer cells, or when recombinant IL‐37 was administered in animal models of cancers (summarized in review papers by Ding et al and Abulkhir et al). However, only limited studies have used cancer patient samples to investigate IL‐37 .…”

Section: Introductionmentioning

confidence: 99%

Interleukin‐37 is highly expressed in regulatory T cells of melanoma patients and enhanced by melanoma cell secretome

Osborne

Domenico

Luo

et al. 2019

Molecular Carcinogenesis

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Immune suppression is one of the 10 hallmarks of cancer. Interleukin‐37 (IL‐37), a member of the IL‐1 family, inhibits both innate and adaptive immunity, and has been shown to modulate immune responses in various disease conditions. Yet, IL‐37 has rarely been investigated in cancer patients, and its biological role in cancer remains to be elucidated. In this study, we investigated the gene expression of IL‐37 in age‐ and sex‐matched blood samples of healthy individuals and melanoma patients, and demonstrated upregulation of IL‐37 messenger RNA (mRNA) in the blood samples of melanoma patients. By further analyzing immune cell subsets responsible for the upregulated IL‐37 expression, we discovered that IL‐37 mRNA was highly expressed in T cells and granulocytes, with the highest expression in regulatory T (Treg) cells in healthy individuals, and that IL‐37 mRNA was upregulated in lymphocytes (T, B, and natural killer cells) in melanoma patient blood. Among all cell subsets, Treg cells from melanoma patients exhibited the highest IL‐37 gene expression levels. We provided evidence that melanoma‐conditioned media induces IL‐37 mRNA and protein expression in multiple lymphocyte populations, particularly in Treg cells. We further confirmed that the IL‐1‐mediated secretome from human melanoma cells, specifically transforming growth factor‐β, induces IL‐37 mRNA expression in human Treg cells. Our results suggest a potential immunosuppressive role for IL‐1 and IL‐37 in melanoma tumorigenesis. Highly elevated IL‐37 in specific lymphocyte populations could serve as a biomarker for tumor‐induced immunosuppression.

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“…STAT3 overexpression restored the CC cell growth and invasion, and increased the transcription of TNF-α and IL-1β (12). IL-37 expression is upregulated in breast carcinoma tissues, which indicates that this cytokine may have a role in tumor progression (9,81). However, IL-37 expression is downregulated in lung cancer tissues and, it suppresses tumorigenesis in non-small cell lung cancer (NSCLC) in vivo.…”

Section: Chronic Inflammatory and Autoimmune Disordersmentioning

confidence: 99%

Interleukin-37: A crucial cytokine with multiple roles in disease and potentially clinical therapy (Review)

et al. 2018

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Abstract. Interleukin (IL)-37, a new IL-1 family member, has received increasing attention in recent years. In the past decade, it has been determined that IL-37 is expressed in various normal cells and tissues and is regulated by inflammatory stimuli and pro-cytokines via different signal transduction pathways. Recently, it has been found that IL-37 is expressed in a variety of cancers, chronic inflammatory and autoimmune disorders, and exerts anti-inflammatory effects. Moreover, a growing body of literature demonstrates that IL-37 plays a vital role in inhibiting both innate and adaptive immune responses as well as inflammatory reactions. In addition, IL-37 may prove to be a new and potentially useful target for effective cytokine therapy. Further evidence is needed to clarify in more detail the effects of IL-37 in experimental and clinical studies. Based on an extensive summary of published data, the aim of this review is to outline the current knowledge of IL-37, including the location, structure, expression, regulation and function, as well as the potential clinical applications of this cytokine.

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The role of IL-37 in cancer

Cited by 36 publications

References 41 publications

IL‐37: An anti‐inflammatory cytokine with antitumor functions

IL‐37: An anti‐inflammatory cytokine with antitumor functions

Interleukin‐37 is highly expressed in regulatory T cells of melanoma patients and enhanced by melanoma cell secretome

Interleukin-37: A crucial cytokine with multiple roles in disease and potentially clinical therapy (Review)

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