Colon cancer-induced interleukin-35 inhibits beta-catenin-mediated pro-oncogenic activity

Jiang, Yuming; Ma, Yanling; Li, RuiChao; Sun, Jiazhong

doi:10.18632/oncotarget.22857

Cited by 12 publications

(9 citation statements)

References 30 publications

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“…These results suggested that IL-35 facilitated cell proliferation of PCA and that decreasing IL-35 was effective at inhibiting the cell proliferation of PCA in vivo. This result is consistent with other studies about IL-35 in breast, colon and pancreas cancers [35][36][37].…”

Section: Discussionsupporting

confidence: 93%

“…In brief, 100 μL of cell suspension (5000 cells) was seeded into each well of a 96-well plate. The plate was incubated for the indicated time periods (12,24,36,48, 60 and 72 h) in an incubator at 37 °C in 5% CO 2 , and 10 μL of CCK-8 solution was added to each well of the plate. The plate was again incubated for 1 h, and the absorbance at 450 nm was measured using a microplate reader.…”

Section: Cell Proliferation Assaymentioning

confidence: 99%

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Interleukin-35 promotes progression of prostate cancer and inhibits anti-tumour immunity

Zhu

Wang

et al. 2020

Cancer Cell Int

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Background Interleukin-35 (IL-35) has been reported to play an important role in the progression of cancers. The role of IL-35 in prostate cancer (PCA) is not well understood. In this study, we investigated the effects of IL-35 on PCA and its immunoregulatory effect on PCA. Methods The protein and mRNA expression of IL-35 in PCA cells was detected by western blot and RT-PCR. The invasion and migration of cells were detected using transwell and wound‐healing assays. A CCK-8 assay was conducted to observe cell proliferation. In vivo, IL-35 plasma concentration was test by enzyme-linked immunosorbent assay. The role of IL-35 in tumour cell proliferation and angiogenesis of mice was detected by immunohistochemical stains. The mouse survival and tumour volumes were calculated, and lung metastasis rate was detected by HE staining. The modulatory effects of IL-35 on myeloid-derived inhibitory cells (MDSCs), regulatory T cells (Tregs), CD4+ T cells and CD8+ T cells from PCA mice were investigated by immunohistochemical stains and flow cytometry. Results High levels of IL-35 significantly promoted the migration, invasion and cell proliferation of PCA cells in vitro. IL-35 was associated with tumour growth, metastasis and poor prognosis in PCA mice. Additionally, high levels of IL-35 significantly increased the proportions of MDSCs and Tregs and decreased the proportions of CD4+ and CD8+ T cells in the spleen, blood and tumour microenvironment. The IL-35 neutralizing antibody played the opposite role. Conclusions IL-35 contributed to the progression of PCA through promoting cell proliferation and tumour angiogenesis. IL-35 might limit the anti-tumour immune response by upregulating the proportions of Tregs and MDSCs and by reducing the proportions of CD4+ and CD8+ T cells. IL-35 might serve as a novel therapeutic target for PCA.

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Section: Discussionsupporting

confidence: 93%

Section: Cell Proliferation Assaymentioning

confidence: 99%

Interleukin-35 promotes progression of prostate cancer and inhibits anti-tumour immunity

Zhu

Wang

et al. 2020

Cancer Cell Int

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“…Notch signaling blockade can also alleviate the inhibitory functions of purified Tregs from gastric carcinoma patients, which can increase the secretion of IL-35, confirming the close feedback relationship between IL-35 and Tregs (50). Intriguingly, IL-35 improve anti-tumor activity via the WNT/ b-catenin pathway, suggesting that IL-35 plays distinct roles in different signaling pathways (51). The activation of the b-catenin pathway has recently been shown to be associated with most human tumors exhibiting spontaneous T cell infiltration (52).…”

Section: Interactions Between Il-35 and T Cells In The Tmementioning

confidence: 69%

IL-35 Regulates the Function of Immune Cells in Tumor Microenvironment

et al. 2021

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Interleukin-35 (IL-35) is a heterodimeric cytokine composed of Epstein-Barr virus-induced gene 3 (EBI3) and IL-12p35 that has recently been shown to play diverse and important roles in the tumor microenvironment (TME). Owing to its immunosuppressive activity and ability to promote tumor growth and progression, IL-35 is widely recognized as a key mediator of TME status. Immune cells are key mediators of diverse tumor-related phenotypes, and immunosuppressive cytokines such as IL-35 can promote tumor growth and metastasis in TME. These influences should be considered together. Since tumor immunotherapy based on immune checkpoint blockade remains ineffective in many patients due to tumoral resistance, a new target or efficacy enhancing factor is urgently needed. Suppressing IL-35 production and activity has been demonstrated as an effective factor that inhibits tumor cells viability, and further investigation of this cytokine is warranted. However, the mechanistic basis for IL-35-mediated regulation of immune cells in the TME remains to be fully clarified. In the present review, we explore the roles of IL-35 in regulating immune cells within the TME. In addition, we highlight IL-35 as a specific immunological target and discuss its possible relevance in the context of immunotherapy. Lastly, we sought to summarize potential future research directions that may guide the advancement of current understanding regarding the role of this important cytokine as a regulator of oncogenesis.

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“…Thus, IL-35 in combination with chemotherapy could be a useful treatment for colon cancer. Similar studies showed that IL-35 plays an inhibitory role in human NSCLC and colon cancer cells by suppressing cell migration and colony formation [188,189]. In hepatocellular carcinoma (HCC) patients, IL-35 expression was significantly reduced in patients with advanced cancer as compared to early stages.…”

Section: Il-35 In Inhibiting Tumor Growthmentioning

confidence: 81%

IL-12 Family Cytokines in Cancer and Immunotherapy

Mirlekar

Pylayeva-Gupta

2021

Cancers

184

102

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The IL-12 family cytokines are a group of unique heterodimeric cytokines that include IL-12, IL-23, IL-27, IL-35 and, most recently, IL-39. Recent studies have solidified the importance of IL-12 cytokines in shaping innate and adaptive immune responses in cancer and identified multipronged roles for distinct IL-12 family members, ranging from effector to regulatory immune functions. These cytokines could serve as promising candidates for the development of immunomodulatory therapeutic approaches. Overall, IL-12 can be considered an effector cytokine and has been found to engage anti-tumor immunity by activating the effector Th1 response, which is required for the activation of cytotoxic T and NK cells and tumor clearance. IL-23 and IL-27 play dual roles in tumor immunity, as they can both activate effector immune responses and promote tumor growth by favoring immune suppression. IL-35 is a potent regulatory cytokine and plays a largely pro-tumorigenic role by inhibiting effector T cells. In this review, we summarize the recent findings on IL-12 family cytokines in the control of tumor growth with an emphasis primarily on immune regulation. We underscore the clinical implications for the use of these cytokines either in the setting of monotherapy or in combination with other conventional therapies for the more effective treatment of malignancies.

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Colon cancer-induced interleukin-35 inhibits beta-catenin-mediated pro-oncogenic activity

Cited by 12 publications

References 30 publications

Interleukin-35 promotes progression of prostate cancer and inhibits anti-tumour immunity

Interleukin-35 promotes progression of prostate cancer and inhibits anti-tumour immunity

IL-35 Regulates the Function of Immune Cells in Tumor Microenvironment

IL-12 Family Cytokines in Cancer and Immunotherapy

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