ArticleInternational immunopharmacology2010
The multikinase inhibitor sorafenib reverses the suppression of IL-12 and enhancement of IL-10 by PGE₂ in murine macrophages.
Article in International immunopharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
48 citing papers in PubMed, 89 citations in OpenAlex.
- Platelet-derived growth factor-C (PDGF-C) induces anti-apoptotic effects on macrophages through Akt and Bad phosphorylation.The Journal of biological chemistry · 2014Trial
- Vitamin B17 alleviates Sorafenib-induced cardiotoxicity in Ehrlich Ascites Carcinoma mice via modulation of inflammatory and fibrotic pathways.Scientific reports · 2025Article
- Engineering strategies of sequential drug delivery systems for combination tumor immunotherapy.Acta pharmaceutica Sinica. B · 2025Review
- Screening immune-related blood biomarkers for DKD-related HCC using machine learning.Frontiers in immunology · 2024Article
- Review
- Sorafenib inhibits LPS-induced inflammation by regulating Lyn-MAPK-NF-kB/AP-1 pathway and TLR4 expression.Cell death discovery · 2022Article
- Advances in CAR-T cell therapy for malignant solid tumors.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2022Review
- Article
- Polypharmacologic Reprogramming of Tumor-Associated Macrophages toward an Inflammatory Phenotype.Cancer research · 2022Article
- Long term complete response of advanced hepatocellular carcinoma to glypican-3 specific chimeric antigen receptor T-Cells plus sorafenib, a case report.Frontiers in immunology · 2022Article
- Review
- Review
- Identification of covalent modifications regulating immune signaling complex composition and phenotype.Molecular systems biology · 2021Article
- The role of macrophages during breast cancer development and response to chemotherapy.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2020Review
- Exploiting Manipulated Small Extracellular Vesicles to Subvert Immunosuppression at the Tumor Microenvironment through Mannose Receptor/CD206 Targeting.International journal of molecular sciences · 2020Review
- Article
- Anti-HER2 induced myeloid cell alterations correspond with increasing vascular maturation in a murine model of HER2+ breast cancer.BMC cancer · 2020Article
- Myeloid-driven mechanisms as barriers to antitumor CD8Molecular immunology · 2020Review
- Targeting Tumor Microenvironment by Small-Molecule Inhibitors.Translational oncology · 2020Review
- Combined Antitumor Effects of Sorafenib and GPC3-CAR T Cells in Mouse Models of Hepatocellular Carcinoma.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Classical activating stimuli like LPS drive macrophages to secrete a battery of inflammatory cytokines, including interleukin (IL)-12/23, through Toll-like receptor (TLR) signaling. TLR activation in the presence of some factors, including prostaglandin E₂ (PGE₂), promotes an anti-inflammatory cytokine profile, with production of IL-10 and suppression of IL-12/23 secretion. Extracellular signal-regulated kinase (ERK) is a key regulator of macrophage IL-10 production. Since it inhibits ERK, we investigated the impact of Sorafenib on the cytokine profile of macrophages. In the presence of PGE₂, Sorafenib restored the secretion of IL-12 and suppressed IL-10 production. Moreover, IL-12 secretion was enhanced by Sorafenib under conditions of TLR ligation alone. Furthermore, the impact of tumor culture supernatants, cholera toxin, and cAMP analogs (which suppress IL-12 secretion), was reversed by Sorafenib. Sorafenib inhibited the activation of the MAP kinase p38 and its downstream target mitogen and stress activated protein kinase (MSK), and partially inhibited protein kinase B (AKT) and its subsequent inactivation of the downstream target glycogen synthase kinase 3-β (GSK3-β). Interference with these pathways, which are pivotal in determining the balance of inflammatory versus anti-inflammatory cytokines, provides a potential mechanism by which Sorafenib can modulate the macrophage cytokine phenotype. These data raise the possibility that the use of Sorafenib as cancer therapy could potentially reverse the immunosuppressive cytokine profile of tumor-associated macrophages, rendering the tumor microenvironment more conducive to an anti-tumor immune response.
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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.