MINI REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1626311
This article is part of the Research TopicFormation and Remodeling of Immunological Niches in Tumors: Organ-Specific Mechanisms and Inflammatory Parallels: Volume IIView all articles
Dual Function of Gasdermin E: Pyroptosis-Mediated Pan-Cancer Suppression versus HCC-Specific Oncogenic Activity
Provisionally accepted
- Hainan Provincial Key Laboratory of Carcinogenesis and Intervention, Hainan Medical University, Haikou, China
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Gasdermin E (GSDME), a key executor of pyroptosis, exerts a unique dual role in tumorigenesis, acting as both a tumor suppressor and a tumor-promoting factor. Due to promoter hypermethylation, GSDME is epigenetically silenced in most solid tumors, including gastric, colorectal, and breast cancers. Its activation triggers the release of inflammatory cytokines, such as IL-1β and IL-18, enhances CD8 + T cell infiltration, and improves chemosensitivity, thereby exerting potent tumorsuppressive effects. Hepatocellular carcinoma (HCC) displays an aberrant GSDME overexpression pattern, which promotes immune suppression and resistance to anti-PD-1 therapy through pyroptosisindependent mechanisms. Notably, specific interventions can activate GSDME-mediated pyroptosis in HCC, highlighting its functional plasticity in response to microenvironmental signaling networks.Current studies face three major challenges: elucidating the mechanisms underlying GSDME overexpression in HCC, clarifying the molecular hubs of pyroptosis-independent pro-tumor pathways, and developing precision strategies to control the functional switch of GSDME. Future studies should integrate single-cell multi-omics and spatial transcriptomics to establish a novel therapeutic paradigm based on "pyroptosis immunomodulation", advancing cancer treatment from single-target inhibition toward multidimensional "microenvironment reprogramming".
Keywords: GSDME, Dual function, pyroptosis, Pan-cancer, HCC
Received: 10 May 2025; Accepted: 28 May 2025.
Copyright: © 2025 Kahaer, Pan, Yang, Xie and Lu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yan Lu, Hainan Provincial Key Laboratory of Carcinogenesis and Intervention, Hainan Medical University, Haikou, China
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