ArticleThe Journal of experimental medicine1999
T helper cell type 1-associated and cytotoxic T lymphocyte-mediated tumor immunity is impaired in interleukin 4-deficient mice.
Article in The Journal of experimental medicine, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 167 citations in OpenAlex.
- Phase I clinical trial with IL-2-transfected xenogeneic cells administered in subcutaneous metastatic tumours: clinical and immunological findings.British journal of cancer · 2000Trial
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- Cellular senescence-related long noncoding ribonucleic acids: Predicting prognosis in hepatocellular carcinoma.Cancer reports (Hoboken, N.J.) · 2023Article
- Comparison of immunophenotypes between Rag2 knockout mice derived from two different sources.Laboratory animal research · 2023Article
- Exploring the regulatory role of lncRNA in cancer immunity.Frontiers in oncology · 2023Review
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- Expression of PD-L1 and CD4+ tumor-infiltrating lymphocytes predict survival in head and neck squamous cell carcinoma.Molecular and clinical oncology · 2022Article
- Nanocages engineered from Bacillus Calmette-Guerin facilitate protective Vγ2Vδ2 T cell immunity against Mycobacterium tuberculosis infection.Journal of nanobiotechnology · 2022Article
- Inflammasome Contribution to the Activation of Th1, Th2, and Th17 Immune Responses.Frontiers in microbiology · 2022Review
- A novel herbal formulation consisting of red ginseng extract andJournal of ginseng research · 2020Article
- Neuronal impairment following chronic Toxoplasma gondii infection is aggravated by intestinal nematode challenge in an IFN-γ-dependent manner.Journal of neuroinflammation · 2019Article
- Activated Natural Killer Cells Mediate the Suppressive Effect of Interleukin-4 on Tumor Development via STAT6 Activation in an Atopic Condition Melanoma Model.Neoplasia (New York, N.Y.) · 2017Article
- Intratumoral Th2 predisposition combines with an increased Th1 functional phenotype in clinical response to intravesical BCG in bladder cancer.Cancer immunology, immunotherapy : CII · 2017Article
- Potent CD4+ T cell-associated antitumor memory responses induced by trifunctional bispecific antibodies in combination with immune checkpoint inhibition.Oncotarget · 2017Article
- Immunosuppression Induced by Chronic Inflammation and the Progression to Oral Squamous Cell Carcinoma.Mediators of inflammation · 2016Article
- IL-4: an important cytokine in determining the fate of T cells.Biophysical reviews · 2014Review
- Deletion of IL-4 receptor alpha on dendritic cells renders BALB/c mice hypersusceptible to Leishmania major infection.PLoS pathogens · 2013Article
- Potential of the trifunctional bispecific antibody surek depends on dendritic cells: rationale for a new approach of tumor immunotherapy.Molecular medicine (Cambridge, Mass.) · 2013Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It is widely accepted that cellular immune responses are induced by CD4(+) T helper 1 (Th1) cells secreting interleukin (IL)-2 and interferon (IFN)-gamma. Tumor immunity is often mediated by cytotoxic T lymphocytes (CTLs) whose activation is supported by Th1 cytokines. Since IL-4 directs Th2 development and has been shown to inhibit Th1-dominated responses, we assumed that IL-4-deficient (IL-4(-/-)) mice would develop vigorous CTL-mediated tumor immunity compared with IL-4-competent (IL-4(+/+)) mice. Surprisingly, IL-4(-/-) mice were severely impaired to develop tumor immunity to both a mammary adenocarcinoma line and a colon carcinoma line. The lack of tumor immunity in IL-4(-/-) mice was associated with reduced IFN-gamma production, diminished levels of tumor-reactive serum IgG2a, and undetectable CTL activity, indicating a defective Th1 response in the absence of endogenous IL-4. Anti-IL-4 monoclonal antibody blocked tumor immunity in IL-4(+/+) mice when administered at the time of immunization but not at the time of challenge. Additionally, tumor immunity could be induced in IL-4(-/-) mice, if IL-4 was provided by gene-modified cells together with immunizing tumor cells. These results demonstrate that tumor immunity requires IL-4 in the priming phase for the generation of effector cells rather than for their maintenance and exclude secondary, developmental defects in the "knockout" strain. Together, our results demonstrate a novel and previously unanticipated role of IL-4 for the generation of Th1-associated, CTL-mediated tumor immunity.
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