ArticleThe Journal of experimental medicine2013
Down-regulation of PLCγ2-β-catenin pathway promotes activation and expansion of myeloid-derived suppressor cells in cancer.
Article in The Journal of experimental medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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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
55 citing papers in PubMed, 81 citations in OpenAlex.
- Trial
- Wnt signaling in cancer: from biomarkers to targeted therapies and clinical translation.Molecular cancer · 2025Review
- MDSC checkpoint blockade therapy: a new breakthrough point overcoming immunosuppression in cancer immunotherapy.Cancer gene therapy · 2025Review
- Role of the Wnt/β-catenin signaling pathway in the development of HCC.Frontiers in immunology · 2025Review
- Review
- DKK-1 and Its Influences on Bone Destruction: A Comparative Study in Collagen-Induced Arthritis Mice and Rheumatoid Arthritis Patients.Inflammation · 2024Article
- Interplay between Signaling Pathways and Tumor Microenvironment Components: A Paradoxical Role in Colorectal Cancer.International journal of molecular sciences · 2023Review
- Modulation of T-cell function by myeloid-derived suppressor cells in hematological malignancies.Frontiers in cell and developmental biology · 2023Review
- Drug discovery of sclerostin inhibitors.Acta pharmaceutica Sinica. B · 2022Review
- Article
- Effective Treatment of Established Bone Metastases Can Be Achieved by Combinatorial Osteoclast Blockade and Depletion of Granulocytic Subsets.Cancer immunology research · 2021Article
- The pancancer landscape of Wnt family expression reveals potential biomarkers in urinary system tumors.Cancer gene therapy · 2021Article
- TGF-β Increases MFGE8 Production in Myeloid-Derived Suppressor Cells to Promote B16F10 Melanoma Metastasis.Biomedicines · 2021Article
- Vesicle transporter GOLT1B mediates the cell membrane localization of DVL2 and PD-L2 and promotes colorectal cancer metastasis.Cancer cell international · 2021Article
- Developmental pathways of myeloid-derived suppressor cells in neoplasia.Cellular immunology · 2021Review
- Myeloid-Derived Suppressor Cells Are a Major Source of Wnt5A in the Melanoma Microenvironment and Depend on Wnt5A for Full Suppressive Activity.Cancer research · 2021Article
- Dickkopf-1: A Promising Target for Cancer Immunotherapy.Frontiers in immunology · 2021Review
- Interferon Regulatory Factor 4 Regulates the Development of Polymorphonuclear Myeloid-Derived Suppressor Cells Through the Transcription of c-Myc in Cancer.Frontiers in immunology · 2021Article
- Manipulating the Wnt/β-catenin signaling pathway to promote anti-tumor immune infiltration into the TME to sensitize ovarian cancer to ICB therapy.Gynecologic oncology · 2021Article
- Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Myeloid-derived suppressor cells (MDSCs) favor tumor promotion, mainly by suppressing antitumor T cell responses in many cancers. Although the mechanism of T cell inhibition is established, the pathways leading to MDSC accumulation in bone marrow and secondary lymphoid organs of tumor-bearing hosts remain unclear. We demonstrate that down-regulation of PLCγ2 signaling in MDSCs is responsible for their aberrant expansion during tumor progression. PLCγ2(-/-) MDSCs show stronger immune-suppressive activity against CD8(+) T cells than WT MDSCs and potently promote tumor growth when adoptively transferred into WT mice. Mechanistically, PLCγ2(-/-) MDSCs display reduced β-catenin levels, and restoration of β-catenin expression decreases their expansion and tumor growth. Consistent with a negative role for β-catenin in MDSCs, its deletion in the myeloid population leads to MDSC accumulation and supports tumor progression, whereas expression of β-catenin constitutively active reduces MDSC numbers and protects from tumor growth. Further emphasizing the clinical relevance of these findings, MDSCs isolated from pancreatic cancer patients show reduced p-PLCγ2 and β-catenin levels compared with healthy controls, similar to tumor-bearing mice. Thus, for the first time, we demonstrate that down-regulation of PLCγ2-β-catenin pathway occurs in mice and humans and leads to MDSC-mediated tumor expansion, raising concerns about the efficacy of systemic β-catenin blockade as anti-cancer 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.