ArticleCellular & molecular immunology2024
Targeting GSDME-mediated macrophage polarization for enhanced antitumor immunity in hepatocellular carcinoma.
Article in Cellular & molecular immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed.
- The gasdermin family: from pyroptosis mechanisms to therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Penfluridol directly targets PDPK1 to suppress AKT1 phosphorylation and stabilize CTR1, inducing cuproptosis in colorectal cancer.Acta pharmacologica Sinica · 2026Article
- Single-cell spatial landscape of aggrephagy activity stratifies hepatocellular carcinoma neutrophils and delivers a 5-gene diagnostic panel for patient stratification.Translational oncology · 2026Article
- Gasdermin E: Bridging Pyroptosis, Immunity, and Disease Pathogenesis Toward Precision Intervention.The protein journal · 2026Review
- P2RY6Cellular oncology (Dordrecht, Netherlands) · 2026Article
- BIRC6 prevents GSDME-mediated pyroptosis and promotes cisplatin resistance via a non-canonical UBC domain-dependent steric hindrance.Cell communication and signaling : CCS · 2026Article
- Integrative Analysis the Role of ENG as a Metabolic and Macrophage-Related Gene in Hepatocellular Carcinoma.Biochemical genetics · 2026Article
- The dual role of pyroptosis in prostate cancer: new perspectives from molecular mechanisms to clinical translation.Molecular biology reports · 2026Review
- Multi-omics analysis of NEDD1 in hepatocellular carcinoma: biological function, prognostic value, and clinical significance.Scientific reports · 2026Article
- Icaritin eliminates tumor-associated macrophages via STX16-dependent extracellular vesicle delivery of autophagosomes from hepatocellular carcinoma cells.Journal of experimental & clinical cancer research : CR · 2026Article
- Programmed cell death inhibitors: a new hope for cancer therapy?World journal of surgical oncology · 2026Review
- Mechanical mechanics-reclaiming a new battlefield for chronic liver disease.Journal of advanced research · 2026Review
- ENPP2 Dysregulation Defines a Candidate Biomarker Axis Coupling Tumor-Intrinsic cAMP Signaling to Macrophage Polarization in Hepatocellular Carcinoma.Human mutation · 2026Article
- Macrophage polarization in gynecologic malignancies: key signaling pathways and clinical perspectives.Frontiers in immunology · 2026Review
- Berberine induces PD-L1 degradation via the autophagy-lysosome pathway through the PI3K-Akt pathway and enhances immunogenic cell death in triple-negative breast cancer.Frontiers in immunology · 2026Article
- Overcoming immune resistance in hepatocellular carcinoma: insights into mechanisms, predictive factors, and interventional strategies.Frontiers in immunology · 2026Review
- Drug resistance mechanisms of immunotherapy and translational strategies for reversing resistance for hepatocellular carcinoma: from bench to bedside.Frontiers in immunology · 2026Review
- Tumor-associated macrophages in cancer: from mechanisms to application.Molecular biomedicine · 2025Review
- Prognostic value of M2 macrophage-related genes and their importance in the immunotherapy response in hepatocellular carcinoma.Oncology letters · 2025Article
- Fosinopril mediates antitumor efficacy by inducing GSDME-dependent pyroptosis in NSCLC.Cell death discovery · 2025Article
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13 authors.
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Abstract
Despite the notable efficacy of anti-PD1 therapy in the management of hepatocellular carcinoma (HCC) patients, resistance in most individuals necessitates additional investigation. For this study, we collected tumor tissues from nine HCC patients receiving anti-PD1 monotherapy and conducted RNA sequencing. These findings revealed significant upregulation of GSDME, which is predominantly expressed by tumor-associated macrophages (TAMs), in anti-PD1-resistant patients. Furthermore, patients with elevated levels of GSDME+ macrophages in HCC tissues presented a poorer prognosis. The analysis of single-cell sequencing data and flow cytometry revealed that the suppression of GSDME expression in nontumor cells resulted in a decrease in the proportion of M2-like macrophages within the tumor microenvironment (TIME) of HCC while concurrently augmenting the cytotoxicity of CD8 + T cells. The non-N-terminal fragment of GSDME within macrophages combines with PDPK1, thereby activating the PI3K-AKT pathway and facilitating M2-like polarization. The small-molecule Eliprodil inhibited the increase in PDPK1 phosphorylation mediated by GSDME site 1. The combination of Eliprodil and anti-PD1 was effective in the treatment of both spontaneous HCC in c-Myc + /+;Alb-Cre + /+ mice and in a hydrodynamic tail vein injection model, which provides a promising strategy for novel combined immunotherapy.
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