ArticleCancer gene therapy2016
Tumor-associated GM-CSF overexpression induces immunoinhibitory molecules via STAT3 in myeloid-suppressor cells infiltrating liver metastases.
Article in Cancer gene therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 113 citations in OpenAlex.
- Review
- Glucose metabolic reprogramming as a driver of immunosuppression in the tumour microenvironment.Clinical and translational medicine · 2026Review
- Article
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- CD301b+ monocyte-derived dendritic cells mediate resistance to radiotherapy.The Journal of experimental medicine · 2025Article
- Comparative evaluation of immunomodulatory cytokines for oncolytic therapy based on a high-efficient platform for oHSV1 reconstruction.Virology journal · 2025Article
- Unlocking the mystery of the PD-1/PD-L1 axis: beyond the checkpoint hype.Frontiers in immunology · 2025Review
- Ultrasound-Mediated Non-Specific Splenic Immunopotentiation to Elicit Broad-Spectrum Anti-Neoplastic Effects.ImmunoTargets and therapy · 2025Article
- Herbal Remedies for Hepatic Inflammation: Unravelling Pathways and Mechanisms for Therapeutic Intervention.Current pharmaceutical design · 2025Review
- Locoregional therapies combined with immune checkpoint inhibitors for liver metastases.Cancer cell international · 2024Review
- Targeting cytokine and chemokine signaling pathways for cancer therapy.Signal transduction and targeted therapy · 2024Review
- Neutrophils in Cancer immunotherapy: friends or foes?Molecular cancer · 2024Review
- Hepatitis B virus-related hepatocellular carcinoma exhibits distinct intratumoral microbiota and immune microenvironment signatures.Journal of medical virology · 2024Article
- Modulation of fracture healing by senescence-associated secretory phenotype (SASP): a narrative review of the current literature.European journal of medical research · 2024Review
- βFrontiers in immunology · 2024Article
- Synergistic antitumor immune response mediated by paclitaxel-conjugated nanohybrid oncolytic adenovirus with dendritic cell therapy.Frontiers in immunology · 2024Article
- Immune Evasion of G-CSF and GM-CSF in Lung Cancer.Tuberculosis and respiratory diseases · 2024Article
- Targeting the myeloid microenvironment in neuroblastoma.Journal of experimental & clinical cancer research : CR · 2023Review
- Exploring the JAK/STAT Signaling Pathway in Hepatocellular Carcinoma: Unraveling Signaling Complexity and Therapeutic Implications.International journal of molecular sciences · 2023Review
- CSF2 upregulates CXCL3 expression in adipocytes to promote metastasis of breast cancer via the FAK signaling pathway.Journal of molecular cell biology · 2023Article
18 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
7 authors at 4 institutions in 1 country.
Funding
Abstract
Assumptions that liver immune cells and immunosuppressive pathways are similar to their counterparts in other spaces have led to gaps in our understanding of intrahepatic neoplasm aggressiveness. Myeloid-derived suppressor cells (MDSCs) are potent inhibitors of antitumor immunity and pose a major obstacle to solid tumor treatment. Liver MDSCs (L-MDSCs) associated with liver metastases (LM) are particularly problematic by contributing to intrahepatic immunosuppression that promotes tumor progression. L-MDSCs have been reported to expand in response to granulocyte-macrophages colony-stimulating factor (GM-CSF) and suppress antitumor immunity in LM. To extend these findings, we examined mechanisms of intrahepatic immunosuppression exploited by L-MDSCs. We found that the majority of L-MDSCs co-expressed GM-CSF receptor (GM-CSF-R), indoleamine 2,3-dioxygenase (IDO) and programmed death ligand 1 (PD-L1), while demonstrating high levels of signal transducer and activator of transcription factor 3 (STAT3) activation. GM-CSF-secreting tumor cells induced STAT3 phosphorylation in L-MDSCs in addition to expression of IDO and PD-L1. GM-CSF or GM-CSF-R blockade markedly reduced L-MDSC IDO and PD-L1 expression, implicating tumor-derived GM-CSF in supporting L-MDSC-immunoinhibitory molecule expression. Small-molecule inhibitors of Janus-activated kinase 2 (JAK2) and STAT3 also dramatically diminished IDO and PD-L1 expression in L-MDSCs. We determined that STAT3 exerts transcriptional control over L-MDSC IDO and PD-L1 expression by binding to the IDO1 and PD-L1 promoters. Our data suggest that the GM-CSF/JAK2/STAT3 axis in L-MDSCs drives immunosuppression in a model of LM and blockade of this pathway may enable rescue of intrahepatic antitumor immunity.
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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.