ArticleJournal for immunotherapy of cancer2025
Unveiling the mechanisms of CEBPD-orchestrated TAM polarization through RGS2/PAR2 pathway and its impact on ICB efficacy in clear cell renal cell carcinoma.
Article in Journal for immunotherapy of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Hesperetin-black phosphorus nanosheets targeting TAMs induce ferroptosis and reverse protumoral polarization to remodel the immune microenvironment.Materials today. Bio · 2026Article
- Bioactive-coated porous anastomotic staples enhance anastomotic healing.Bioactive materials · 2026Article
- Immune Escape in Renal Cell Carcinoma: Latest Research and Treatment Strategies.International journal of molecular sciences · 2026Review
- Stiripentol directly attenuates immunosuppression of tumor-infiltrating myeloid cells to potentiate anti-PD-1 efficacy.BMC cancer · 2026Article
- Transcriptional activation of ALOX5 by c-Myc drives malignant progression and M2 macrophage polarization in clear cell renal cell carcinoma.American journal of cancer research · 2026Article
- circPVT1 regulates EMT and induces macrophage polarization to promotes the progression of renal cell carcinoma.Frontiers in immunology · 2026Article
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Abstract
backgroundThe polarization status and function of tumor-associated macrophages (TAMs) influence tumor progression and patients' prognosis. CCAAT/enhancer-binding proteins (CEBPs) family are important transcriptional factors in macrophages differentiation physically and pathologically. This study aims to explore the mechanism of CEBPs in TAMs polarization in clear cell renal cell carcinoma (ccRCC) immune microenvironment and its impact on immune checkpoint blockers (ICBs) therapy.
methodsThe expression of CEBPs in ccRCC was analyzed by single-cell transcriptome and western blot. Immunofluorescence and in-vitro polarization assay were used to evaluate the effect of CEBP delta (CEBPD) on TAMs. Chromatin immunoprecipitation sequencing was used to explore targets of CEBPD. Dual-luciferase reporter assay and electrophoretic mobility shift assay were performed to confirm the regulation of CEBPD to RGS2. Specimens of patients received ICB therapy were used to analyze the relationship between CEBPD and immunotherapy.
resultsThe study identified CEBPD as a key transcriptional factor in ccRCC TAM polarization. Upregulation of CEBPD correlates to decreased M1/M2 ratio of TAMs and poorer clinical outcomes. CEBPD inhibited M1-like polarization in vitro and in vivo via the RGS2/PAR2 axis. Furthermore, CEBPD also affected the therapeutic efficacy of ICB.
conclusionThis study revealed CEBPD regulated TAM polarization via the CEBPD/RGS2/PAR2 axis. Targeting CEBPD may be a potential approach and a complementary strategy to ICB therapies in ccRCC.
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