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

Wu, Wei; Jiang, Hua; Li, Ying; Yan, Mao-Xiao

doi:10.3892/ol.2017.5858

Cited by 10 publications

(10 citation statements)

References 29 publications

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“…IL-35 has led many scholars to study its expression regulation, molecular signalling and immunoregulation. Recent studies have shown that IL-35 is overexpressed in a variety of tumours [ 24 – 27 ]. It can be used directly in tumour cells to regulate the expression of related proteins, and it also plays an important role in the occurrence and development of tumours by inducing the production of regulatory T cells, inhibiting the response of effector T cells, regulating anti-tumour immune response and inducing immune escape [ 10 , 28 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

“…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: Discussionmentioning

confidence: 99%

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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“…It is reported that B cells 21 and tumor‐associated macrophages 22 could also secrete IL‐35 in cancer. High serum level of IL‐35 was always associated with worse prognosis in several cancer types, such as nonsmall cell lung cancer, 23 breast cancer, 24 prostate cancer, 25 laryngeal squamous cell carcinoma, 26 and hepatocellular carcinoma 27 …”

Section: Discussionmentioning

confidence: 99%

“…anti-inflammatory and immunosuppressive factor. 16,17 Although has been reported to be involved in plenty of pathological processes such as inflammatory diseases and autoimmune diseases, 18,19 cancer, 24 prostate cancer, 25 laryngeal squamous cell carcinoma, 26 and hepatocellular carcinoma. 27 The association between IL-35 and GC prognosis has not been clari- 29,30 The main function of FOXP3+ Tregs is secreting cytokines including IL-35, and they are highly expressed in HP-positive patients than in HP-negative patients.…”

Section: Association Between Serum Il-35 and Prognosis Of Gcmentioning

confidence: 99%

Serum level of interleukin‐35 as a potential prognostic factor for gastric cancer

Wang

et al. 2020

Asia-Pac J Clncl Oncology

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Aims Interleukin‐35 (IL‐35), a novel anti‐inflammatory cytokine, has recently been implicated in tumor development, progression, and survival. However, the relationship between serum IL‐35 levels and gastric cancer (GC) is inconclusive. Here, we performed this study to clarify the role of serum level of IL‐35 in GC patients. Methods We enrolled 180 GC patients and 170 healthy controls and used enzyme‐linked immunosorbent assay to detect serum IL‐35 levels. The clinical relevance between IL‐35 and clinical pathology parameters was assessed. Univariate and multivariate logistic regressions were used to determine the feasibility of IL‐35 as a clinical biomarker. Results We observed that serum IL‐35 levels were significantly higher in GC patients (17.559 ± 13.266 pg/mL) than in healthy controls (8.077 ± 3.801 pg/mL, P < .001). High serum IL‐35 levels were significantly associated with clinical stage (P = .048) and Helicobacter pylori (HP) infection (P < .001). The Kaplan‐Meier survival analysis indicated that patients in the high‐IL‐35 group had poor overall survival (OS) and progression‐free survival (PFS) (median OS: 26.0 vs 36.0 months, P < .001; median PFS: 18.0 vs.26.0 months, P = .044). Multivariate analyses demonstrated that serum IL‐35 was an independent prognostic factor for GC (OS: hazard ratio [HR] = 1.031 [95% CI, 1.017‐1.045], P < .001; PFS: HR = 1.029 [95% CI, 1.015‐1.043], P < .001). Conclusions High serum IL‐35 levels are associated with poor disease prognosis in GC patients, and it may be become a new and promising biomarker for prognosis of gastric cancer.

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“…IL-35 is composed of an Epstein-barr virus-induced gene 3 (EBI3) subunit and IL-12A (p35) subunit (6). Previous studies demonstrated that IL-35 expression was increased in a variety of tumor tissues, including pancreatic ductal adenocarcinoma (PDAC), colorectal cancer, renal cell carcinoma and laryngeal squamous cell cancer (7–10). Furthermore, IL-35 was demonstrated to promote tumor angiogenesis and inhibit the anti-tumor cytotoxic lymphocyte response (11).…”

Section: Introductionmentioning

confidence: 99%

Interleukin‑35 is associated with the tumorigenesis and progression of prostate cancer

et al. 2019

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Interleukin (IL)-35 is a novel member of the IL-12 cytokine family, which exhibits a unique immune regulatory function. Previously, it was demonstrated that IL-35 expression is significantly increased in a wide range of tumor tissues, promoting angiogenesis and inhibiting the anti-tumor immune response. In the present study, the IL-35 protein expression levels were measured in the plasma and tumor tissue of patients with prostate cancer (PCA), and its role was determined in the occurrence and progression of PCA. Plasma IL-35 expression levels were measured using ELISA, and the associations of plasma IL-35 and clinicopathological parameters were analyzed. Receiver operating characteristic curves were plotted to analyze the role of IL-35 as a clinical biomarker for the diagnosis of PCA. Survival curve analysis demonstrated a significant decrease in the survival time in months in patients with PCA and increased expression levels of IL-35 compared with the participants with relatively lower IL-35 protein expression levels. IL-35 expression was detected using immunohistochemical staining of a human PCA tissue microarray. Plasma IL-35 expression levels in the patients with PCA were significantly increased compared with the patients with benign prostatic hyperplasia and the healthy controls. An increase in the plasma concentration of IL-35 was associated with progression of PCA stage and an increase in the Gleason score. Significant differences in AUCs for IL-35 and prostate-specific antigen were observed with regard to the presence of lymph node and distant metastases in patients with PCA. The expression levels of Epstein-barr virus-induced gene 3 (EBI3) and IL-12A (p35; the subunits which together form IL-35) were significantly increased in the tumor tissue compared with the adjacent normal tissue. An association was identified between the Gleason score and the expression of EBI3 and p35. Therefore, increased expression of IL-35 in the plasma and tumor tissues may contribute to the progression and metastasis of PCA, and IL-35 may serve as a novel prognostic biomarker or therapeutic target for the treatment of PCA.

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

Cited by 10 publications

References 29 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

Serum level of interleukin‐35 as a potential prognostic factor for gastric cancer

Interleukin‑35 is associated with the tumorigenesis and progression of prostate cancer

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