ArticleOncotarget2016
Elevated level of interleukin-35 in colorectal cancer induces conversion of T cells into iTr35 by activating STAT1/STAT3.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Systematic Review of Interleukin-35 in Endothelial Dysfunction: A New Target for Therapeutic Intervention.Mediators of inflammation · 2025Pooled it
- The expression patterns of Interleukin-26, Interleukin-35, and signal transducer and activator of transcription 1 in Type1 diabetes patients with diabetic nephropathy.Molecular biology reports · 2026Article
- iTr35 cells: a novel immunoregulatory subset involved in bone loss in rheumatoid arthritis and clinical implications.Annals of medicine · 2025Article
- Interleukin-35 impairs human NK cell effector functions and induces their ILC1-like conversion with tissue residency features.Nature communications · 2025Article
- Dendrobium huoshanense polysaccharide inhibits NSCLC proliferation and immune evasion via FXR1-IL-35 axis signaling pathway.Journal of natural medicines · 2025Article
- Immunomodulatory activity of 4-(Benzyloxy)phenol facilitates intracellular mycobacterial clearance through p53 mediated IL-35 signaling dependent JAK1/STAT3 pathway in human macrophages.Immunologic research · 2025Article
- The recombinant IL-35 and anti-Ebi3 antibody administration before implantation modulate immune regulation and fetal outcomes in an abortion-prone mouse model.Frontiers in immunology · 2025Article
- The role of CD8Heliyon · 2024Review
- Immunomodulatory effects of iTr35 cell subpopulation and its research progress.Clinical and experimental medicine · 2024Review
- Immunological mechanisms of tolerance: Central, peripheral and the role of T and B cells.Asia Pacific allergy · 2023Review
- Human IL-35 Inhibits the Bioactivity of IL-12 and Its Interaction with IL-12Rβ2.ImmunoHorizons · 2023Article
- Interleukin-35 promotes Breg expansion and interleukin-10 production in CD19Clinical rheumatology · 2022Article
- Level of interleukin-35 in patients with idiopathic membranous nephropathy and its predictive value for remission time.Frontiers in immunology · 2022Article
- Colorectal Cancer-Infiltrating Regulatory T Cells: Functional Heterogeneity, Metabolic Adaptation, and Therapeutic Targeting.Frontiers in immunology · 2022Review
- IL-12 Family Cytokines in Cancer and Immunotherapy.Cancers · 2021Review
- IL-35 Regulates the Function of Immune Cells in Tumor Microenvironment.Frontiers in immunology · 2021Review
- Aberrant Th2 Immune Responses Are Associated With a Reduced Frequency of IL-35-Induced Regulatory T Cells After Allergen Exposure in Patients With Allergic Asthma.Allergy, asthma & immunology research · 2020Article
- Review
- Interleukin-35 sensitizes monocytes from patients with asthma to glucocorticoid therapy by regulating p38 MAPK.Experimental and therapeutic medicine · 2020Article
- Increased Interleukin-35 suppresses peripheral CD14BMC immunology · 2020Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
IL-35 is a novel heterodimeric and inhibitory cytokine, composed of interleukin-12 subunit alpha (P35) and Epstein-Barr virus -induced gene 3 (EBI3). IL-35 has been reported to be produced by a range of cell types, especially regulatory T cells, and to exert immunosuppressive effects via the STATx signaling pathway. In this study, we demonstrated that IL-35 expression was elevated in both serum and tumors in patients with colorectal cancer. IL-35 mainly expressed in CD4+ T cells in human colorectal cancer tumors and adjacent tissues. Increased IL-35 expression in tumor-adjacent tissues was significantly associated with tumor metastasis. IL-35 inhibited the proliferation of CD4+CD25- T effector cells in vitro in a dose-dependent manner, and its suppression was partially reversed by applying IL-35-neutralizing antibodies. IL-35 treatment activated the phosphorylation of both STAT1 and STAT3 in human CD4+ T cells. Meanwhile, IL-35 induced a positive feedback loop to promote its own production. We observed that Tregs obtained from colorectal cancer patients were capable of inducing more IL-35 production. In addition, EBI3 promoter-driven luciferase activity was higher than that of the mock plasmid after IL-35stimulation. Thus, our study indicates that the high level of IL-35 in colorectal cancer promotes the production of IL-35 via STAT1 and STAT3, which suppresses T cell proliferation and may participate in tumor immunotolerance.
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