Interleukin-35 Expression in Non-Small Cell Lung Cancer is Associated with Tumor Progression

Sun, Ming‐Zhong; Zheng, Xiaoting; Meng, Qingjiang; Dong, Yuchao; Zhang, Guoyu; Rao, D.K.; An, Xiaokang; Yang, Zhi-Chun; Pan, Lihong; Zhang, Shuanglin

doi:10.1159/000495706

Cited by 5 publications

(4 citation statements)

References 19 publications

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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: 76%

IL-12 Family Cytokines in Cancer and Immunotherapy

Mirlekar

Pylayeva-Gupta

2021

Cancers

179

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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Section: Il-35 In Inhibiting Tumor Growthmentioning

confidence: 76%

IL-12 Family Cytokines in Cancer and Immunotherapy

Mirlekar

Pylayeva-Gupta

2021

Cancers

179

102

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“…In human patient samples, decreased IL-35 expression was observed in cancer sites compared to non-cancer sites. Through the use of NSCLC cell lines, this study demonstrated that IL-35 treatment resulted in suppressed beta-catenin expression and decreased migration, invasion, and proliferation of the cancer cells (148). Therefore IL-35 may behave similarly to IL-27 to have divergent roles in cancer progression that may be dependent on cancer type, stage, and TME landscape.…”

Section: Il-27 Il-30 and Il-35: Influencing Cancer Developmentmentioning

confidence: 92%

“…The primary function of IL-35 within the TME appears to be in favor of a pro-tumor immune environment. In contrast to the work discussed above, Sun et al outlined a potential anti-tumor role for IL-35 in NSCLC (148). In human patient samples, decreased IL-35 expression was observed in cancer sites compared to non-cancer sites.…”

Section: Il-27 Il-30 and Il-35: Influencing Cancer Developmentmentioning

confidence: 97%

IL-27, IL-30, and IL-35: A Cytokine Triumvirate in Cancer

et al. 2019

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The role of the immune system in anti-tumor immunity cannot be overstated, as it holds the potential to promote tumor eradication or prevent tumor cell escape. Cytokines are critical to influencing the immune responses and interactions with non-immune cells. Recently, the IL-12 and IL-6 family of cytokines have accumulated newly defined members each with specific immune functions related to various cancers and tumorigenesis. There is a need to better understand how cytokines like IL-27, IL-30, and IL-35 interact with one another, and how a developing tumor can exploit these interactions to enhance immune suppression. Current cytokine-based immunotherapies are associated with cytotoxic side effects which limits the success of treatment. In addition to this toxicity, understanding the complex interactions between immune and cancer cells may be one of the greatest challenges to developing a successful immunotherapy. In this review, we bring forth IL-27, IL-30, and IL-35, “sister cytokines,” along with more recent additions to the IL-12 family, which serve distinct purposes despite sharing structural similarities. We highlight how these cytokines function in the tumor microenvironment by examining their direct effects on cancer cells as well their indirect actions via regulatory functions of immune cells that act to either instigate or inhibit tumor progression. Understanding the context dependent immunomodulatory outcomes of these sister cytokines, as well as their regulation within the tumor microenvironment, may shed light onto novel cancer therapeutic treatments or targets.

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“…It has been illustrated that IL-35 inhibits T cells proliferation and transforms T cells into suppressive inducible Tregs ( 3 ). Recently, some studies have demonstrated the expression of IL-35 is correlated with tumor progression, including breast cancer, NSCLC and prostate cancer ( 5 , 6 , 13 ). Moreover, our previous study found that IL-35 is expressed highly in the peripheral blood and tumor tissues of patients with LSCC ( 8 ).…”

Section: Discussionmentioning

confidence: 99%

IL-35 inhibits CD8+ T cells activity by suppressing expression of costimulatory molecule CD28 and Th1 cytokine production

Jiang

Zhang

Yan

et al. 2019

Transl. Cancer Res.

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Background Interleukin-35 (IL-35), a novel immune-suppressing cytokine, can promote tumor angiogenesis and inhibits anti-tumor cytotoxic lymphocyte response. Here, we aimed to investigate the potential mechanism of the effects of IL-35 on anti-tumor cytotoxic lymphocyte. Methods Dendritic cells (DCs) were used to induce anti-tumor cytotoxic lymphocyte. Flow cytometry, carboxyfluorescein succinimidyl ester staining, ELISA assay and western blotting were used to analyze the effect of IL-35 on anti-tumor cytotoxic lymphocyte. Results We observed that IL-35 inhibited the expression of costimulatory molecule CD28 on CD8 + T cell surface and Th1 cytokine production. However, IL-35 did not inhibit anti-tumor cytotoxic lymphocyte proliferation nor enhance the expression of apoptosis-related proteins of anti-tumor cytotoxic lymphocyte. Moreover, IL-35 did not repress the expression of Fas ligand (FasL) on cytotoxic lymphocyte surface. Conclusions Our findings revealed that IL-35 can inhibit CD8 + T cells activity by suppressing the expression of costimulatory molecule CD28 and Th1 cytokine production.

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Interleukin-35 Expression in Non-Small Cell Lung Cancer is Associated with Tumor Progression

Cited by 5 publications

References 19 publications

IL-12 Family Cytokines in Cancer and Immunotherapy

IL-12 Family Cytokines in Cancer and Immunotherapy

IL-27, IL-30, and IL-35: A Cytokine Triumvirate in Cancer

IL-35 inhibits CD8+ T cells activity by suppressing expression of costimulatory molecule CD28 and Th1 cytokine production

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