ArticleCell death discovery2023
Midkine inhibition enhances anti-PD-1 immunotherapy in sorafenib-treated hepatocellular carcinoma via preventing immunosuppressive MDSCs infiltration.
Article in Cell death discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- Midkine restrains T-cell mediated anti-tumor immunity by suppressing macrophage M1 polarization in lung adenocarcinoma.Translational cancer research · 2026Article
- Rewiring immunity: Midkine's emerging role in cancer immune escape and drug resistance.iScience · 2026Review
- Midkine (MDK) as a central regulator of the tumor microenvironment: From developmental cytokine to therapeutic target.Cancer letters · 2026Review
- Overcoming MDSC-Mediated Immunosuppression in Hepatocellular Carcinoma: From Mechanisms to Novel Immunotherapeutic Approaches.Cancers · 2026Review
- Midkine as a therapeutic node in NF1-driven neuro‑oncology: Biology, biomarkers, and translational strategies.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Review
- The Discovery and Characterization of HBS-101, a Novel Inhibitor of Midkine, as a Therapeutic Agent for the Treatment of Triple-Negative Breast Cancer.Molecular cancer therapeutics · 2025Article
- Metabolic reprogramming of arachidonic acid in clear cell renal carcinoma promotes an immunosuppressive microenvironment by activating MDK signaling pathway.Clinical and experimental medicine · 2025Article
- From preneoplastic lesion to heterogenous tumor: recent insights into hepatoblastoma biology and therapeutic opportunities.Molecular cancer · 2025Review
- Viral-Track integrated single-cell RNA-sequencing reveals HBV lymphotropism and immunosuppressive microenvironment in HBV-associated hepatocellular carcinoma.Communications biology · 2025Article
- Midkine Promotes Tumor Growth and Attenuates the Effect of Cisplatin in Small Cell Lung Cancer.Cancer medicine · 2025Article
- Blocking the functional domain of cancer cell surface TIP1 upregulates Midkine via the β-catenin/Wnt signaling pathway.Cancer gene therapy · 2025Article
- Significance of Midkine Signaling in Women's Cancers: Novel Biomarker and Therapeutic Target.International journal of molecular sciences · 2025Review
- Blocking MIF secretion enhances CAR T-cell efficacy against neuroblastoma.European journal of cancer (Oxford, England : 1990) · 2025Article
- Sorafenib enhanced the function of myeloid-derived suppressor cells in hepatocellular carcinoma by facilitating PPARα-mediated fatty acid oxidation.Molecular cancer · 2025Article
- RNA Interference based Midkine Gene Therapy for Hepatocellular Carcinoma.Asian Pacific journal of cancer prevention : APJCP · 2024Article
- PPP1R15A-expressing monocytic MDSCs promote immunosuppressive liver microenvironment in fibrosis-associated hepatocellular carcinoma.JHEP reports : innovation in hepatology · 2024Article
- Overview of the immunological mechanisms in hepatitis B virus reactivation: Implications for disease progression and management strategies.World journal of gastroenterology · 2024Review
- TheCancers · 2024Review
- Nasopharynx Battlefield: Cellular Immune Responses Mediated by Midkine in Nasopharyngeal Carcinoma and COVID-19.Cancers · 2023Review
- Role of Midkine in Cancer Drug Resistance: Regulators of Its Expression and Its Molecular Targeting.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sorafenib, a multiple-target tyrosine kinase inhibitor, is the standard of care for patients with advanced hepatocellular carcinoma (HCC), but provides limited benefits. Emerging evidences suggest that prolonged sorafenib treatment induces an immunosuppressive HCC microenvironment, but the underling mechanism is undetermined. In the present study, the potential function of midkine, a heparin-binding growth factor/cytokine, was evaluated in sorafenib-treated HCC tumors. Infiltrating immune cells of orthotopic HCC tumors were measured by flow cytometry. Differentially expressed genes in sorafenib-treated HCC tumors were evaluated by transcriptome RNA sequencing. The potential function of midkine were evaluated by western blot, T cell suppression assay, immunohistochemistry (IHC) staining and tumor xenograft model. We found that sorafenib treatment increased intratumoral hypoxia and altered HCC microenvironment towards an immune-resistant state in orthotopic HCC tumors. Sorafenib treatment promoted midkine expression and secretion by HCC cells. Moreover, forced midkine expression stimulated immunosuppressive myeloid-derived suppressor cells (MDSCs) accumulation in HCC microenvironment, while knockdown of midkine exhibited opposite effects. Furthermore, midkine overexpression promoted CD11b
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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.