ArticleOncogene2019
STAT3 inhibition induces Bax-dependent apoptosis in liver tumor myeloid-derived suppressor cells.
Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 124 citations in OpenAlex.
- The Erk/CREB Signaling Axis Mediates G-CSF-Promoted G-MDSC Survival in the Peripheral Blood of Melanoma-Bearing Mice.Biology · 2026Article
- mRNA lipid-nanoparticle-mediated mitochondrial apoptosis augments adoptive T cell immunotherapy.Cell reports. Medicine · 2026Article
- Article
- Macrophage-delivered Nifuroxazide reprograms immunosuppressive microenvironment and synergizes with oxaliplatin for enhanced anti-hepatocellular carcinoma therapy.Journal of nanobiotechnology · 2026Article
- STAT3 signaling in cancer: mechanisms and targeting therapeutic.Frontiers in immunology · 2026Review
- TFF3 initiates gastric intestinal metaplasia by activating JAK2 and STAT3 under high salt conditions.Scientific reports · 2025Article
- Myeloid-Derived Suppressor Cells in Cancer: Mechanistic Insights and Targeted Therapeutic Innovations.MedComm · 2025Review
- Research on the functions and potential mechanisms of STAT3 in chronic myelogenous leukemia.Discover oncology · 2025Article
- Myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment and their targeting in cancer therapy.Molecular cancer · 2025Review
- Pressure enabled drug delivery (PEDD) of nelitolimod increased therapeutic delivery, reduced immunosuppression, and improved efficacy in porcine and murine liver tumor models.Frontiers in oncology · 2025Article
- [Myeloid-derived suppressor cells as important factors and potential targets for breast cancer progression].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2024Review
- Unlocking Apoptotic Pathways: Overcoming Tumor Resistance in CAR-T-Cell Therapy.Cancer medicine · 2024Review
- Harnessing the tumor microenvironment to boost adoptive T cell therapy with engineered lymphocytes for solid tumors.Seminars in immunopathology · 2024Review
- Subcutaneous checkpoint inhibition is equivalent to systemic delivery when combined with nelitolimod delivered via pressure-enabled drug delivery for depletion of intrahepatic myeloid-derived suppressor cells and control of liver metastases.Journal for immunotherapy of cancer · 2024Article
- Understanding the immunosuppressive microenvironment of glioma: mechanistic insights and clinical perspectives.Journal of hematology & oncology · 2024Review
- Listeria-vectored cervical cancer vaccine candidate strains reduce MDSCs via the JAK-STAT signaling pathway.BMC biology · 2024Article
- Myeloid‑derived suppressor cell accumulation induces Treg expansion and modulates lung malignancy progression.Biomedical reports · 2024Article
- Immunotherapy Innovations in the Fight against Osteosarcoma: Emerging Strategies and Promising Progress.Pharmaceutics · 2024Review
- The Roles of Myeloid-Derived Suppressor Cells in Liver Disease.Biomedicines · 2024Review
- TP53 to mediate immune escape in tumor microenvironment: an overview of the research progress.Molecular biology reports · 2024Review
20 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Immunosuppressive myeloid-derived suppressor cells (MDSC) subvert antitumor immunity and limit the efficacy of chimeric antigen receptor T cells (CAR-T). Previously, we reported that the GM-CSF/JAK2/STAT3 axis drives liver-associated MDSC (L-MDSC) proliferation and blockade of this axis rescued antitumor immunity. We extended these findings in our murine liver metastasis (LM) model, by treating tumor-bearing mice with STAT3 inhibitors (STATTIC or BBI608) to further our understanding of how STAT3 drives L-MDSC suppressive function. STAT3 inhibition caused significant reduction of tumor burden as well as L-MDSC frequencies due to decrease in pSTAT3 levels. L-MDSC isolated from STATTIC or BBI608-treated mice had significantly reduced suppressive function. STAT3 inhibition of L-MDSC was associated with enhanced antitumor activity of CAR-T. Further investigation demonstrated activation of apoptotic signaling pathways in L-MDSC following STAT3 inhibition as evidenced by an upregulation of the pro-apoptotic proteins Bax, cleaved caspase-3, and downregulation of the anti-apoptotic protein Bcl-2. Accordingly, there was also a decrease of pro-survival markers, pErk and pAkt, and an increase in pro-death marker, Fas, with activation of downstream JNK and p38 MAPK. These findings represent a previously unrecognized link between STAT3 inhibition and Fas-induced apoptosis of MDSCs. Our findings suggest that inhibiting STAT3 has potential clinical application for enhancing the efficacy of CAR-T cells in LM through modulation of L-MDSC.
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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.