ArticleBlood2011
Acquired STAT4 deficiency as a consequence of cancer chemotherapy.
Article in Blood, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- Article
- An Immunomodulating Peptide with Potential to Promote Anticancer Immunity Without Compromising Immune Tolerance.Biomedicines · 2025Article
- miR-200a-3p predicts prognosis and inhibits bladder cancer cell proliferation by targeting STAT4.Archives of medical science : AMS · 2023Article
- Genetic associations of T cell cancer immune response-related genes with T cell phenotypes and clinical outcomes of early-stage lung cancer.Journal for immunotherapy of cancer · 2020Article
- A Dose-escalation Study of Recombinant Human Interleukin-18 in Combination With Ofatumumab After Autologous Peripheral Blood Stem Cell Transplantation for Lymphoma.Journal of immunotherapy (Hagerstown, Md. : 1997) · 2018Article
- Vitamin D Impacts the Expression of Runx2 Target Genes and Modulates Inflammation, Oxidative Stress and Membrane Vesicle Biogenesis Gene Networks in 143B Osteosarcoma Cells.International journal of molecular sciences · 2017Article
- Clinicopathological significance of STAT4 in hepatocellular carcinoma and its effect on cell growth and apoptosis.OncoTargets and therapy · 2016Article
- Decreased STAT4 indicates poor prognosis and enhanced cell proliferation in hepatocellular carcinoma.World journal of gastroenterology · 2015Article
- Modulatory effects of bortezomib on host immune cell functions.Immunotherapy · 2015Review
- Signal transducer and activator of transcription 4 in liver diseases.International journal of biological sciences · 2015Review
- The natural product phyllanthusmin C enhances IFN-γ production by human NK cells through upregulation of TLR-mediated NF-κB signaling.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Soypeptide lunasin in cytokine immunotherapy for lymphoma.Cancer immunology, immunotherapy : CII · 2014Article
- Article
- The oncoprotein HBXIP uses two pathways to up-regulate S100A4 in promotion of growth and migration of breast cancer cells.The Journal of biological chemistry · 2012Article
- A dose-escalation study of recombinant human interleukin-18 in combination with rituximab in patients with non-Hodgkin lymphoma.Journal of immunotherapy (Hagerstown, Md. : 1997)Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Signal Transducer and Activator of Transcription 4 (STAT4) is a transcription factor that is activated by IL-12 signaling and promotes Th1-cell differentiation and IFN-γ production. Defective IFN-γ production because of STAT4 mRNA and protein deficiency occurs after autologous stem cell transplantation for lymphoma. In the present study, we investigated the mechanisms of STAT4 deficiency in lymphoma patients. The tumor-bearing state is not responsible, because STAT4 levels were not significantly different in PBMCs obtained from healthy control subjects compared with those from lymphoma patients before treatment. STAT4 protein levels were significantly decreased in PBMCs and T cells obtained from lymphoma patients after standard-dose chemotherapy. Furthermore, treatment of control PBMC cultures or a natural killer cell line with chemotherapy drugs in vitro also resulted in reduced STAT4 protein and diminished, IL-12-induced IFN-γ production. Translation of STAT4 protein was not impaired in chemotherapy-treated cells, whereas the STAT4 protein half-life was significantly reduced. Chemotherapy drugs promoted the ubiquitination and proteasomal degradation of STAT4. Treatment with the proteasome inhibitor bortezomib reversed chemotherapy-induced STAT4 deficiency and defective IFN-γ production. We conclude that acquired STAT4 deficiency in lymphoma patients is a consequence of treatment with chemotherapy, results that have important implications for the design of optimal immunotherapy for lymphoma.
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