{
  "abstract": "Background & Aims: Local ablation triggers an antitumor response and is regarded as an encouraging treatment combined with immunotherapy for hepatocellular carcinoma (HCC). Irreversible electroporation (IRE) is a novel ablative technique eliminating tumor cells by electroporation, however, the characteristics of IRE-induced immune microenvironment and underlying mechanism remain unclear.\n\nMethods: We developed an orthotopic immunocompetent HCC mouse model and performed incomplete IRE-ablation. The post-IRE immune microenvironment was characterized by RNA sequencing, single-cell RNA sequencing, flow cytometry, and multiplex immunofluorescence. Cytokine-chemokine array and organoid-immune cell co-culture were used to investigate the functions and underlying mechanism. The combination therapy of IRE and anti-programmed cell death protein 1 (PD-1) was examined for HCC treatment in mice.\n\nResults: IRE initially inhibited HCC growth, but tumors rapidly regrew by day 14 after ablation, with increased Ly6G+ polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) infiltration and CD8+ T-cell exhaustion. In patient-derived HCC organoids, IRE-induced CD8+ T-cell cytotoxicity was suppressed by myeloid-derived suppressor cells (MDSCs). Ly6G antibody-mediated PMN-MDSCs depletion repressed HCC regrowth after IRE-ablation in vivo (1.29 ± 0.12 vs 0.49 ± 0.09 g, p <0.001). Mechanistically, HCC cells degraded CXCL10 mRNA via YTH N6-methyladenosine RNA binding protein F2 (YTHDF2), which activated MDSCs that led to CD8+ T-cell exhaustion. Combined anti-PD-1 and IRE reduced tumor burden by 84.6% compared with IRE alone (0.22 ± 0.08 vs 1.43 ± 0.13 g, p <0.01), prolonged survival (40-day survival: 60% vs 6.7%, p <0.001), and induced long-term antitumor immunity in mice. Four patients with unresectable recurrent HCC treated with IRE plus anti-PD-1 therapy showed improved recurrence-free time than patients receiving IRE alone.\n\nConclusions: PMN-MDSCs mediated immunosuppression that promoted HCC regrowth after incomplete IRE-ablation. Combining anti-PD-1 therapy is a promising approach to eliminate post-ablation residual HCC, supporting evaluation in prospective clinical trials.\n\nImpact and implications: Post-ablation recurrence remains a major challenge in HCC. Here, we show that although IRE initially activates CD8+ T cells but subsequently promotes PMN-MDSCs activation and CD8+ T-cell exhaustion through YTHDF2-mediated CXCL10 mRNA degradation, resulting in a suppressive tumor immune microenvironment. These findings identify a previously unrecognized mechanism of post-IRE tumor regrowth and provide a rationale for early combination with anti-PD-1 therapy. Although further prospective clinical validation is required, this work suggests that monitoring post-ablation immune changes and applying rational immunotherapy combinations may help optimize treatment strategies for patients with HCC undergoing local ablation.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Oncology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China",
    "Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China",
    "Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China",
    "Department of Urology Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China",
    "Department of Rheumatology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China",
    "Department of Gastroenterology and Hepatology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China",
    "Division of Interventional Ultrasound, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China",
    "Clinical Trials Unit, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China",
    "Center of Hepato-Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China",
    "Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong Province, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 20,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jihui Huo"
    },
    {
      "affs": [
        1
      ],
      "name": "Lina Wang"
    },
    {
      "affs": [
        2
      ],
      "name": "Kai Lei"
    },
    {
      "affs": [
        1
      ],
      "name": "Weishan Luo"
    },
    {
      "affs": [
        3
      ],
      "name": "Zongren Wang"
    },
    {
      "affs": [
        4
      ],
      "name": "Hongtao Zhu"
    },
    {
      "affs": [
        0
      ],
      "name": "Gaomin Zheng"
    },
    {
      "affs": [
        1
      ],
      "name": "Youmei Kang"
    },
    {
      "affs": [
        1
      ],
      "name": "Wenjie Huang"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaoxue Ren"
    },
    {
      "affs": [
        5
      ],
      "name": "Yingdong Hou"
    },
    {
      "affs": [
        1
      ],
      "name": "Cong Liang"
    },
    {
      "affs": [
        0
      ],
      "name": "Tao Yang"
    },
    {
      "affs": [
        6
      ],
      "name": "Manxia Lin"
    },
    {
      "affs": [
        1
      ],
      "name": "Xiaoxing Li"
    },
    {
      "affs": [
        1,
        5,
        7
      ],
      "name": "Sui Peng"
    },
    {
      "affs": [
        1,
        8,
        9
      ],
      "name": "Ming Kuang"
    },
    {
      "affs": [
        6
      ],
      "name": "Han Xiao"
    },
    {
      "affs": [
        6
      ],
      "name": "Shuling Chen"
    },
    {
      "affs": [
        8
      ],
      "name": "Zihao Dai"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cs771jx4cd58q.bib",
  "cited_by": 0,
  "doi": "10.1016/j.jhepr.2026.101977",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13743422/",
  "id": "cs771jx4cd58q",
  "issns": [
    "2589-5559"
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  "landing_url": "https://doi.org/10.1016/j.jhepr.2026.101977",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research Article"
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      "openalex",
      "2730|Cancer Immunotherapy and Biomarkers"
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  "pdf_url": "https://www.jhep-reports.eu/article/S2589-5559(26)00248-X/pdf",
  "pmcid": "PMC13743422",
  "pmid": "42546925",
  "published": "2026-08-03",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/cs771jx4cd58q.ris",
  "sources": [
    {
      "first_seen": "2026-11-10T12:24:10Z",
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      "source": "pmc",
      "url": "https://doi.org/10.1016/j.jhepr.2026.101977"
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cancer Immunotherapy and Biomarkers",
      "subfield": "oncology"
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  ],
  "title": "Combined anti-PD-1 with irreversible electroporation relieves immunosuppression and reduces hepatocellular carcinoma regrowth",
  "title_text": "Combined anti-PD-1 with irreversible electroporation relieves immunosuppression and reduces hepatocellular carcinoma regrowth",
  "type": "peer-reviewed",
  "updated_at": "2026-11-11T12:21:08Z",
  "url": "https://research.draconitic.com/paper/cs771jx4cd58q",
  "venue": "JHEP Reports",
  "versions": []
}