Increased P-35, EBI3 Transcripts and Other Treg Markers in Peripheral Blood Mononuclear Cells of Breast Cancer Patients with Different clinical Stages

Hamidinia, Maryam; Boroujerdnia, Mehri Ghafourian; Talaiezadeh, Abdolhassan; Solgi, Ghasem; Roshani, R; Iranprast, Sara; Khodadadi, Ali

doi:10.15171/apb.2015.036

Cited by 23 publications

(34 citation statements)

References 32 publications

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“…In the clinical field of breast cancer, increased expression of EBI3 has always been found in tumor samples [20,23]. Besides, the IL-23/IL-35 cytokine ratio was proved to be associated with poor prognosis of breast cancer [20].…”

Section: Discussionmentioning

confidence: 99%

Upregulated EBI3 Correlates with Poor Outcome and Tumor Progression in Breast Cancer

Jiang

Liu

2018

Oncol Res Treat

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Background and Aim: So far, the understanding of the role of Epstein-Barr virus-induced gene 3 (EBI3) in breast cancer has been limited. This study uncovers the functional role and clinical significance of EBI3 in breast cancer patients. Patients and Methods: The expression levels of EBI3, IL-27p28, and IL-12p35 were measured by quantitative real-time reverse transcription (RT)-polymerase chain reaction (PCR). Correlations of EBI3 expression with IL-27p28 and IL-12p35 expression were analyzed using Pearson's correlation assay. The prognostic performance of EBI3 was assessed via Kaplan-Meier survival assay and Cox regression analysis. Results:EBI3 expression was increased in cancerous tissues compared with the controls (P < 0.05). This overexpression of EBI3 was correlated with lymph node metastasis and clinical stage (both P < 0.05). Besides, elevated expression of EBI3 was usually found in patients with positive lymph node metastasis (P < 0.05), and similar results were obtained in advanced clinical-stage breast cancer cases (P < 0.05). Increases in both IL-27p28 and IL-12p35 expression were identified in breast cancer tissues (all P < 0.05), and IL-12p35 expression was found to be associated with EBI3 expression (R = 0.888, P < 0.001). Survival curves revealed that high EBI3 expression was correlated with poor overall survival (log-rank P < 0.05). The Cox analysis indicated that EBI3 was an independent prognostic factor in breast cancer. Conclusion: Taken together, overexpression of EBI3 was associated with poor prognosis and might be involved in the progression of breast cancer.

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Section: Discussionmentioning

confidence: 99%

Upregulated EBI3 Correlates with Poor Outcome and Tumor Progression in Breast Cancer

Jiang

Liu

2018

Oncol Res Treat

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“…In previous studies, over-expression of IL-35 in peripheral blood has been recognized as an unfavorable prognostic factor for malignant tumors, including nasopharyngeal carcinoma, pancreatic ductal adenocarcinoma, colorectal and non-small cell lung cancer (14,21,28,29). Nevertheless, another study detected increased IL-35 expression in early stage breast cancer and non-metastatic cases (27).…”

Section: The Association Between Il-35 Expression and The Prognosis Omentioning

confidence: 98%

IL-35 expression is increased in laryngeal squamous cell carcinoma and in the peripheral blood of patients

Jiang

et al. 2017

Oncology Letters

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Abstract. has been proposed as a novel immune-suppressing cytokine. However, the function of IL-35 in malignant diseases is yet to be elucidated. The present study investigated IL-35 expression levels in laryngeal squamous cell carcinoma (LSCC) tissues and the peripheral blood of patients to explore the potential involvement of IL-35 in LSCC progression. In the present study, IL-35 expression levels in tissues and peripheral blood were analyzed by reverse transcription-quantitative polymerase chain reaction and an enzyme-linked immunosorbent assay. The association between IL-35 expression levels and clinical characteristics was also evaluated. The present results demonstrated that IL-35 expression in tumor tissues was significantly higher than in adjacent normal tissues, and a significant association between IL-35 expression levels in tissues and the tumor site was detected. Furthermore, the expression of IL-35 in the peripheral blood of patients was significantly decreased subsequent to tumor resection. No correlation between peripheral blood IL-35 expression and clinical characteristics was detected. In conclusion, the present study demonstrated that IL-35 is highly expressed in LSCC tissues and in the peripheral blood of patients with LSCC. There was a notable, significant reduction of peripheral blood IL-35 expression following surgical resection of tumors. These results may be useful for diagnostic or therapeutic purposes in patients with LSCC.

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“…Accordingly, both Treg cell depletion and T effector cell stimulation have been explored extensively and manifested anti‐tumor promising results. Regarding IL‐35, this cytokine has been monitored together with other regulatory cytokines as an indicator of Treg cell activity …”

Section: Il‐35 Regulatory Cells and Other Mediatorsmentioning

confidence: 99%

“…20,27 Treg cells comprise 5% to 10% of CD4 1 T cells; however, their role in regulation of immune outcomes is significant. 57 Treg cells can be divided into two main subtypes: naturally occurring, thymic-derived CD4 1 CD25 1 Treg cells (nTreg) and peripherally antigen-induced CD4 1 CD25 2 T cells, which are derived from na€ ıve CD4 1 T cell precursors after TGF-b or IL-10 stimulation. 57 Depending on the stimulus (e.g., TGF-b or IL-10), these peripherally na€ ıve T cells have been shown to be converted to either TGF-b-producing forkhead box P3 (Foxp3)-expressing (CD4 1 Foxp3 1 ) inducible T regulatory (iTreg) or IL10-producing CD4 1 Foxp3 2 iTr1 cells in vitro, respectively.…”

Section: Il-35 Regulatory Cells and Other Mediatorsmentioning

confidence: 99%

IL‐35, a hallmark of immune‐regulation in cancer progression, chronic infections and inflammatory diseases

Teymouri

Pirro

Fallarino

et al. 2018

Intl Journal of Cancer

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Cytokine members of the IL-12 family have attracted enormous attention in the last few years, with IL-35 being the one of the most attractive-suppressive cytokine. IL-35 is an important mediator of regulatory T cell function. Regulatory T cells play key roles in restoring immune homeostasis after facing challenges such as infection by specific pathogens. Moreover, a crucial role for regulatory T cell populations has been demonstrated in several physiological processes, including establishment of fetal-maternal tolerance, maintenance of self-tolerance and prevention of autoimmune diseases. However, a deleterious involvement of immune regulatory T cells has been documented in specific inhibition of immune responses against tumor cells, promotion of chronic infections and establishment of chronic inflammatory disorders. In this review, we attempt to shed light on the concept of immune-homoeostasis on the aforementioned issues, taking IL-35 as the hallmark of regulatory responses. The dilemma between immune-mediated cancer treatment and inflammation is discussed. Histopathological indications of chronic vs. acute infections are elaborated. Moreover, the evidence that IL-35 requires additional immune-regulatory cytokines, such as IL-10 and TGF-β, to induce effective and maximal anti-inflammatory effects suggest that immune-regulation requires multi-factorial analysis of many immune playmakers rather than a specific immune target.

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Increased P-35, EBI3 Transcripts and Other Treg Markers in Peripheral Blood Mononuclear Cells of Breast Cancer Patients with Different clinical Stages

Cited by 23 publications

References 32 publications

Upregulated <b><i>EBI3</i></b> Correlates with Poor Outcome and Tumor Progression in Breast Cancer

Upregulated <b><i>EBI3</i></b> Correlates with Poor Outcome and Tumor Progression in Breast Cancer

IL-35 expression is increased in laryngeal squamous cell carcinoma and in the peripheral blood of patients

IL‐35, a hallmark of immune‐regulation in cancer progression, chronic infections and inflammatory diseases

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