Elevated IL-35 in bone marrow of the patients with acute myeloid leukemia

Jia, Wang; Tao, Qianshan; Wang, Huiping; Wang, Zhitao; Wu, Fan; Pan, Ying; Tao, Lili; Xiong, Sheng; Wang, Yiping; Zhai, Zhimin

doi:10.1016/j.humimm.2015.09.020

Cited by 27 publications

(15 citation statements)

References 26 publications

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“…Likewise, circulating levels of plasma IL-35 were higher in PDAC along with correlated increase in IL-35 mRNA expression and worsening tumor stage 61. Elevated levels of IL-35 in bone marrow, peripheral blood plasma and TME of patients with Acute Myeloid Leukemia (AML) are also reported 62-65. An important clinical study put forward by Zhao and colleagues described the data from 60 breast invasive ductal carcinoma (IDC) patients and confirmed the presence of robust IL-35 expression in tumor infiltrating lymphocytes (TILs).…”

Section: Evidences Of Il-35 In Cancer Developmentmentioning

confidence: 98%

Interleukin-35 as an Emerging Player in Tumor Microenvironment

Xue¹,

Yan²,

Kan³

2019

J. Cancer

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IL-35 is the newest member of IL-12 family. A dimeric protein consisting of two separate subunits has manifested suppressive actions on immune system, which is counterproductive in the context of cancers. Various reports have confirmed its inhibitory role on immune system which is carried out via formation of IL-35-producing regulatory T cells (iTr35), increased Treg development and suppressive Th17 cells growth. Although last decade has seen a great deal of scientific interest on this subject, the exact role, precise signal transduction and elaborative functions of IL-35 in tumor microenvironment (TME) remained elusive. Search for anti-IL-35 therapies have exhibited limited success in animal models. Contrarily, few studies have denied the idea that IL-35 plays a role in cancer. The purpose of this review is to analyze the reported scientific data on continuous symphony of IL-35 in cancers since the inception of former.

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Section: Evidences Of Il-35 In Cancer Developmentmentioning

confidence: 98%

Interleukin-35 as an Emerging Player in Tumor Microenvironment

Xue¹,

Yan²,

Kan³

2019

J. Cancer

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“…Perhaps not surprisingly, contrary to autoimmune conditions, expression of IL35 has been implicated in promoting tumorigenesis (Table 1; cancer, and pancreatic cancer (52)(53)(54). Increase in tumorinfiltrating IL35 þ T cells and Bregs has now also been reported in melanoma, colorectal cancer, and pancreatic cancer (8,50).…”

Section: Clinical-translational Advancesmentioning

confidence: 99%

Molecular Pathways: Interleukin-35 in Autoimmunity and Cancer

Pylayeva-Gupta

2016

Clinical Cancer Research

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Immunosuppressive functions conferred by regulatory cytokines are important for maintaining homeostasis in immune responses. IL35 has recently emerged as a novel regulator of immune responses. Once thought to be specifically expressed by T regulatory cells, induction of IL35 expression has now been detected in multiple cell types in a variety of diseases, prompting research into regulation of its expression, signaling specificity, target cell populations, and functional outputs. Recent studies have revealed that by directing de novo generation of regulatory T and B cells and inhibiting T effector responses, IL35 plays an important role in the development of autoimmune diseases and cancer. IL35 is overexpressed in a variety of cancers and may exert its function both on antitumor immune responses as well as directly on tumor cells. As such, IL35 is rapidly emerging as a promising biomarker and an attractive cancer therapy target. Clin Cancer Res; 22(20); 4973-8. ©2016 AACR.

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“…To investigate which cell types express IL-35 in DLBCL, we tested different commercial Abs for IL-35 detection by immunohistochemistry. In several published immunohistochemical studies of IL-35 expression in human cancers including hepatocellular carcinomas, colorectal cancer or breast cancer, the expression of IL-35 heterodimer was investigated by using a commercial mouse anti-IL-35 mAb (clone 15k8D10, original supplier Imgenex) (7, 20–22, 24, 32). This mAb, raised against a fusion protein formed of human EBI3 and p35 subunits fused to the Fc domain of human IgG1, was initially described as specific for IL-35 and later indicated to be specific for EBI3 subunit by immunoblot or immunohistochemical analyses of paraffin-embedded human tissues.…”

Section: Resultsmentioning

confidence: 99%

Evidence for IL-35 Expression in Diffuse Large B-Cell Lymphoma and Impact on the Patient's Prognosis

et al. 2019

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IL-35 is an immunosuppressive cytokine of the IL-12 family consisting of two subunits, EBV-induced gene 3 (EBI3) and p35. It has been shown to play a pro-tumor role in murine tumor models, and in various types of human cancer such as colorectal, pancreatic, or liver carcinoma, its expression has been associated with a worse clinical outcome. Here, we show by analyzing gene expression data from public databases and by immunohistochemical studies that IL-35 is overexpressed by tumor cells in diffuse-large B-cell lymphoma (DLBCL) compared to another type of mature aggressive B-cell lymphoma, Burkitt lymphoma. However, while high IL-35 expression was significantly associated with a worse overall survival in DLBCL patients treated with chemotherapy only (cyclophosphamide, doxorubicin, vincristine, prednisone, CHOP), no significant correlation between IL-35 expression levels and the patient outcome was observed in DLBCL patients treated with CHOP combined to rituximab (R-CHOP), the current conventional treatment. In addition, we found that an anti-IL-35 antibody, clone 15k8D10, used to assess IL-35 expression by immunohistochemistry in various human tissues including tumors does not recognize IL-35 heterodimer, nor its individual subunits EBI3 and p35, but cross-reacts with human IgG1, indicating that IL-35 expression in human cancers needs to be re-evaluated.

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Elevated IL-35 in bone marrow of the patients with acute myeloid leukemia

Cited by 27 publications

References 26 publications

Interleukin-35 as an Emerging Player in Tumor Microenvironment

Interleukin-35 as an Emerging Player in Tumor Microenvironment

Molecular Pathways: Interleukin-35 in Autoimmunity and Cancer

Evidence for IL-35 Expression in Diffuse Large B-Cell Lymphoma and Impact on the Patient's Prognosis

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