ArticleCell death and differentiation2023
Transcription factor Zhx2 is a checkpoint that programs macrophage polarization and antitumor response.
Article in Cell death and differentiation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 19 citations in OpenAlex.
- Transcription factors remodel tumor immune microenvironment by impacting multiple immune cells.Discover oncology · 2026Review
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- The Transcription Factor DDIT3 Regulates Macrophage Function by Inhibiting KLF10 to Attenuate ALI/ARDS Inflammation.Inflammation · 2026Article
- Engrailed 1 promotes immune evasion and chemoresistance in glioma through single cell and CeRNA network analyses.Scientific reports · 2026Article
- Metabolic symbiosis and competition: the dual nature of TAM-tumor cell cross-talk in tumor progression.Frontiers in oncology · 2026Review
- Rewiring tumor immunity via zinc finger proteins: a new frontier in cancer immunotherapy.Journal of translational medicine · 2025Review
- Baicalin attenuates the immune escape of oral squamous cell carcinoma by reducing lactate accumulation in tumor microenvironment.Journal of advanced research · 2025Article
- Immune microenvironment in hepatocellular carcinoma: from pathogenesis to immunotherapy.Cellular & molecular immunology · 2025Review
- Prognostic Significance of HMGA1 in Hepatocellular Carcinoma: Implications for Tumor Progression and Targeted Therapy.Archives of Iranian medicine · 2025Article
- Liquid-liquid phase separation of ZHX2 protects DLBCL cells against ferroptosis through induction of SLC3A2.Leukemia · 2025Article
- Targeting tumor-associated macrophages to overcome immune checkpoint inhibitor resistance in hepatocellular carcinoma.Journal of experimental & clinical cancer research : CR · 2025Review
- The Regulatory Network of Transcription Factors in Macrophage Polarization.ImmunoTargets and therapy · 2025Review
- β-Hydroxybutyrate suppresses M1 macrophage polarization through β-hydroxybutyrylation of the STAT1 protein.Cell death & disease · 2024Article
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- ZNF740 facilitates the malignant progression of hepatocellular carcinoma via the METTL3/HIF‑1A signaling axis.International journal of oncology · 2024Article
- Tumor‑associated macrophages activated in the tumor environment of hepatocellular carcinoma: Characterization and treatment (Review).International journal of oncology · 2024Review
- Immune-response gene 1 deficiency aggravates inflammation-triggered cardiac dysfunction by inducing M1 macrophage polarization and aggravating Ly6CBiology direct · 2024Article
- Review
- Role of tumor-associated macrophages in hepatocellular carcinoma: impact, mechanism, and therapy.Frontiers in immunology · 2024Review
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Macrophages are usually educated to tumor-associated macrophages (TAMs) in cancer with pro-tumor functions by tumor microenvironment (TME) and TAM reprogramming has been proposed as a potential tumor immunotherapy strategy. We recently demonstrated the critical role of Zinc-fingers and homeoboxes 2 (Zhx2) in macrophages' metabolic programming. However, whether Zhx2 is responsible for macrophage polarization and TAMs reprogramming is largely unknown. Here, we show that Zhx2 controls macrophage polarization under the inflammatory stimulus and TME. Myeloid-specific deletion of Zhx2 suppresses LPS-induced proinflammatory polarization but promotes IL-4 and TME-induced anti-inflammatory and pro-tumoral phenotypes in murine liver tumor models. Factors in TME, especially lactate, markedly decrease the expression of Zhx2 in TAMs, leading to the switch of TAMs to pro-tumor phenotype and consequent cancer progression. Notably, reduced ZHX2 expression in TAM correlates with poor survival of HCC patients. Mechanistic studies reveal that Zhx2 associates with NF-κB p65 and binds to the Irf1 promoter, leading to transcriptional activation of Irf1 in macrophages. Zhx2 functions in maintaining macrophage polarization by regulating Irf1 transcription, which may be a potential target for macrophage-based cancer immunotherapy.
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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.