Interleukin-35 Dampens CD8+ T Cells Activity in Patients With Non-viral Hepatitis-Related Hepatocellular Carcinoma

Yang, Lijing; Shao, Xue; Jia, Shengnan; Zhang, Qian; Jin, Zhenjing

doi:10.3389/fimmu.2019.01032

Cited by 31 publications

(31 citation statements)

References 34 publications

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“…Upon exposure of purified CD4 + or CD8 + T cell populations to recombinant IL-35, both populations exhibited reduced cytotoxicity (143). Additionally, CD8 + T cells from patients with non-viral hepatitis-related hepatocellular carcinoma (HCC) showed a decrease in cytotoxic function when treated with recombinant IL-35 (144). Similarly, human breast cancer cells produce IL-35 which functions to convert conventional T cell populations to iTr35 cells (145).…”

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

confidence: 99%

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

confidence: 99%

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

et al. 2019

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“…In contrast to the cytokines discussed above, increases in IL-35 are due to the presence of regulatory T cells (Tregs) and regulatory B cells (Bregs) [61]. Treg cells can promote the production of new Treg cells by inducing the transformation of Treg (iTreg) from CD4+Foxp3-T cells [62].…”

Section: Anti-viral Functionsmentioning

confidence: 99%

Immunoregulatory Functions of the IL-12 Family of Cytokines in Antiviral Systems

Guo

Cao

Zhu

2019

Viruses

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Members of the interleukin 12 (IL-12) family have been known to be inflammatory factors since their discovery. The IL-12 family consists of IL-12, IL-23, IL-27, IL-35, and a new member, IL-39, which has recently been identified and has not yet been studied extensively. Current literature has described the mechanisms of immunity of these cytokines and potential uses for therapy and medical cures. IL-12 was found first and is effective in combatting a wide range of naturally occurring viral infections through the upregulation of various cytokines to clear the infected cells. IL-23 has an essential function in immune networks, can induce IL-17 production, and can antagonize inhibition from IL-12 in the presence of T helper (Th) 17 cells, resulting in type II IFN (IFN-γ) regulation. IL-27 has a competitive relationship to IL-35 because they both include the same subunit, the Epstein–Barr virus-induced gene3 (EBi3). This review provides a simple introduction to the IL-12 family and focuses on their functions relevant to their actions to counteract viral infections.

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“…Cytokines have been demonstrated to mediate these reactions, including IL-12 family of cytokines. The family encompasses five cytokines; IL-6, IL-12, IL-23, IL-27 and IL-35, which have been reported to play a vital role in the development of HBV [6,21,22] and other infections [23]. IL-35 is a newly described cytokine in this family, but its role in HBV infection has not been well-investigated.…”

Section: Resultsmentioning

confidence: 99%

Serum Level of Interleukin-35 in Patients with Chronic Hepatitis B Virus Infection

Al-azzawi

Mohsen

Ad’hiah

2020

eijs

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Interleukin-35 (IL-35) is a new member of IL-12 family of cytokines, and its role in pathogenesis of hepatitis B virus (HBV) infection has been recently suggested. Accordingly, a case-control study was conducted during June - October 2018 to determine IL-35 serum level in Iraqi patients with chronic HBV infection. The results revealed that IL-35 level was significantly decreased in patients as compared to control (163 vs. 301 pg/ml; p < 0.001). However, such decreased level was more pronounced in patients at the age groups < 40 and 40 – 50 years (165 and 145 pg/ml, respectively) as compared to the corresponding age groups in control (482 and 234 pg/ml, respectively). In the case of gender groups, both male and female patients showed a significantly decreased level of IL-35 compared to the corresponding control groups (163 and 163 vs. 306 and 297 pg/ml; p = 0.004 and 0.001, respectively). Distributing HBV patients and control according to medians of IL-35 (≤ median and > median) revealed that 67.5% of patients had ≤ median compared to 35.4% among control. Such difference was significant (p < 0.001), with a scored odds ratio (OR) of 3.79. Receiver operating characteristic (ROC) analysis revealed that the decreased level of IL-35 occupied an area under curve (AUC) of 0.710, which was highly significant (p < 0.001). At a cut-value of 188 pg/ml or lower, the diagnostic sensitivity and specificity were 67.7 and 66.2%, respectively. In conclusion, these results confirmed the role of IL-35 in the pathogenesis of HBV

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Interleukin-35 Dampens CD8+ T Cells Activity in Patients With Non-viral Hepatitis-Related Hepatocellular Carcinoma

Cited by 31 publications

References 34 publications

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

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

Immunoregulatory Functions of the IL-12 Family of Cytokines in Antiviral Systems

Serum Level of Interleukin-35 in Patients with Chronic Hepatitis B Virus Infection

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