ArticleOncotarget2017
IL-35 induces N2 phenotype of neutrophils to promote tumor growth.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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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
68 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- Systematic Review of Interleukin-35 in Endothelial Dysfunction: A New Target for Therapeutic Intervention.Mediators of inflammation · 2025Pooled it
- CHAC2-mediated glutathione metabolic reprogramming drives N1 polarization of bone marrow neutrophils and exacerbates inflammatory comorbidities.International journal of oral science · 2026Article
- Dynamic regulation and targeted intervention of neutrophils in hepatic ischemia‑reperfusion injury (Review).International journal of molecular medicine · 2026Review
- Interleukin 35 promotes progression of hepatocellular carcinoma by recruiting neutrophils.Translational oncology · 2026Article
- Recruitment of neutrophils by granulocyte colony-stimulating factor in cancer patients undergoing immunotherapy: the good, the bad, and the unknown.Frontiers in immunology · 2026Review
- Cancer cells metastasize in several types of cancer via two distinct routes, probably based on mechanical signals.Frontiers in cell and developmental biology · 2026Review
- The role of neutrophils in bronchiectasis.Annals of medicine · 2025Review
- Neutrophils in non-small cell lung cancer and immunotherapy with PD-1/PD-L1 inhibitors.Journal of translational medicine · 2025Review
- Review
- Therapeutic potential of tumor-associated neutrophils: dual role and phenotypic plasticity.Signal transduction and targeted therapy · 2025Review
- The complement system and kidney cancer: pathogenesis to clinical applications.The Journal of clinical investigation · 2025Review
- Harnessing myeloid cells in cancer.Molecular cancer · 2025Review
- 4-Phenyl Butyric Acid (4-PBA) Suppresses Neutrophil Recruitment in a Murine Model of Acute Perinatal Inflammation.Journal of immunology research · 2025Article
- Targeting innate and adaptive immunity to suppress lung cancer metastasis.Frontiers in immunology · 2025Review
- Retrospective analysis of inflammatory biomarkers and prognosis in non-small cell lung cancer without adenocarcinoma in situ.Frontiers in genetics · 2025Article
- Cytokine-induced transcriptional changes in human neutrophils reveal immune regulatory plasticity.Discovery immunology · 2025Article
- Focus on Pancreatic Cancer Microenvironment.Current oncology (Toronto, Ont.) · 2024Review
- Review
- Preoperative systemic immune-inflammation index-based nomogram for lung carcinoma following microwave ablation -a real world single center study.Frontiers in oncology · 2024Article
- Immunological mechanisms of tolerance: Central, peripheral and the role of T and B cells.Asia Pacific allergy · 2023Review
8 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
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
IL-35 is an immunosuppressive cytokine and exerts regulatory effects on T cells, B cells, macrophages and dendritic cells. Neutrophils are important innate immune cells that play key roles in tumor development. The effect of IL-35 on neutrophils remains unknown. Here, we report that IL-35 can induce N2 neutrophil polarization (protumor phenotype) by increasing G-CSF and IL-6 production, and promote neutrophil infiltration into tumor microenvironment. The sustained expression of IL-35 could promote chronic inflammation to augment the proangiogenic and immunosuppressive function of neutrophils. IL-35 stimulated macrophages to secrete proinflammatory cytokines IL-1β and IL-6. IL-1β stimulated γδ T cells to produce IL-17, which in turn increased the production of G-CSF. By increasing the expression of G-CSF and IL-6, IL-35 could up-regulate the expression of MMP-9 and Bv8, and down-regulate TRAIL expression in neutrophils, thus augmenting the proangiogenic function of neutrophils. Moreover, G-CSF/IL-6 induced the enhanced activation of STAT3 and ERK pathways in neutrophils, thus increasing the expression of iNOS to suppress T cell activation. Our findings suggest that IL-35 can promote tumor progression by functioning as an up-stream cytokine to promote cancer-associated inflammation and control neutrophil polarization. Targeting IL-35 might be an important approach for designing new strategy of tumor therapy.
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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.