ArticleJournal of immunology (Baltimore, Md. : 1950)2013
Tumor-derived IL-35 promotes tumor growth by enhancing myeloid cell accumulation and angiogenesis.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
94 citing papers in PubMed, 2 syntheses or guidelines pooled it, 157 citations in OpenAlex.
- Systematic Review of Interleukin-35 in Endothelial Dysfunction: A New Target for Therapeutic Intervention.Mediators of inflammation · 2025Pooled it
- The role of chemokines and interleukins in acute lymphoblastic leukemia: a systematic review.Journal of applied biomedicine · 2024Pooled it
- Overexpression of interleukin-35 associates with hepatocellular carcinoma aggressiveness and recurrence after curative resection.British journal of cancer · 2016Trial
- Spatial and phenotypic plasticity of B cells in remodeling the tumor microenvironment.Journal for immunotherapy of cancer · 2026Review
- Serum Interleukin-35 Levels in Oral Squamous Cell Carcinoma and Salivary Gland Tumors: Implications for Early Detection and Prognosis.BioMed research international · 2026Article
- Role of serum IL-35 levels in patients with benign and malignant primary ovarian tumors: a case-control study.Scientific reports · 2025Article
- The distinct role of IL-34 and IL-35 in gastric cancer.Frontiers in immunology · 2025Review
- Regulation of Treg cells by cytokine signaling and co-stimulatory molecules.Frontiers in immunology · 2024Review
- Human interleukin-12α and EBI3 are cytokines with anti-inflammatory functions.Science advances · 2023Article
- Human IL-35 Inhibits the Bioactivity of IL-12 and Its Interaction with IL-12Rβ2.ImmunoHorizons · 2023Article
- Apelin receptor antagonist boosts dendritic cell vaccine efficacy in controlling angiogenic, metastatic and apoptotic-related factors in 4T1 breast tumor-bearing mice.Medical oncology (Northwood, London, England) · 2023Article
- Head and Neck Cancer Immunotherapy: Molecular Biological Aspects of Preclinical and Clinical Research.Cancers · 2023Review
- How the Tumor Micromilieu Modulates the Recruitment and Activation of Colorectal Cancer-Infiltrating Lymphocytes.Biomedicines · 2022Review
- Mechanisms of induction of regulatory B cells in the tumour microenvironment and their contribution to immunosuppression and pro-tumour responses.Clinical and experimental immunology · 2022Review
- Systems biology of angiogenesis signaling: Computational models and omics.WIREs mechanisms of disease · 2022Review
- Review
- The Molecular Role of IL-35 in Non-Small Cell Lung Cancer.Frontiers in oncology · 2022Review
- Elevated Plasma Interleukin-35 as a Prognostic Indicator in Localized Clear Cell Renal Cell Carcinoma.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- The role of IL-35 and IL-37 in breast cancer - potential therapeutic targets for precision medicine.Frontiers in oncology · 2022Review
- The role of B cells in the development, progression, and treatment of lymphomas and solid tumors.Advances in immunology · 2022Review
34 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
IL-35 is a member of the IL-12 family of cytokines that is comprised of an IL-12 p35 subunit and an IL-12 p40-related protein subunit, EBV-induced gene 3 (EBI3). IL-35 functions through IL-35R and has a potent immune-suppressive activity. Although IL-35 was demonstrated to be produced by regulatory T cells, gene-expression analysis revealed that it is likely to have a wider distribution, including expression in cancer cells. In this study, we demonstrated that IL-35 is produced in human cancer tissues, such as large B cell lymphoma, nasopharyngeal carcinoma, and melanoma. To determine the roles of tumor-derived IL-35 in tumorigenesis and tumor immunity, we generated IL-35-producing plasmacytoma J558 and B16 melanoma cells and observed that the expression of IL-35 in cancer cells does not affect their growth and survival in vitro, but it stimulates tumorigenesis in both immune-competent and Rag1/2-deficient mice. Tumor-derived IL-35 increases CD11b(+)Gr1(+) myeloid cell accumulation in the tumor microenvironment and, thereby, promotes tumor angiogenesis. In immune-competent mice, spontaneous CTL responses to tumors are diminished. IL-35 does not directly inhibit tumor Ag-specific CD8(+) T cell activation, differentiation, and effector functions. However, IL-35-treated cancer cells had increased expression of gp130 and reduced sensitivity to CTL destruction. Thus, our study indicates novel functions for IL-35 in promoting tumor growth via the enhancement of myeloid cell accumulation, tumor angiogenesis, and suppression of tumor immunity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.