{
  "abstract": "Hepatocellular carcinoma (HCC) is characterized by low expression of major histocompatibility complex class I (MHC‐I), which significantly limits the efficacy of immunotherapy. In this work, bioinformatic analysis finds that elevated PCSK9 in HCC correlates with reduced T cell activity and poor prognosis. Based on these discoveries, a PD‐L1 nanobody‐engineered synthetic RNA virus (αPDL1‐VLPs/shPCSK9) is fabricated to inhibit PCSK9, thereby restoring MHC‐I expression to enhance HCC immunotherapy. The αPDL1‐VLPs/shPCSK9 is produced using MS2 virus‐like particles (VLPs) in Escherichia coli (E. coli), displaying PD‐L1 nanobodies and encapsulating PCSK9‐downregulating shRNA. Notably, αPDL1‐VLPs/shPCSK9 upregulates MHC‐I to enhance cytotoxic T lymphocytes (CTLs) recognition of tumor cells while promoting M2‐to‐M1 macrophages polarization, thereby boosting immunotherapy. In vivo studies indicate that αPDL1‐VLPs/shPCSK9 exhibits HCC tumor‐targeting behavior, suppressing primary tumor growth while avoiding systemic toxicity. Immunological analysis confirms that αPDL1‐VLPs/shPCSK9 enhances CTLs activation and infiltration, triggering systemic antitumor immunity to eradicate distant tumors. Overall, these findings highlight αPDL1‐VLPs/shPCSK9 as a promising therapeutic strategy for reversing the multiple immunosuppressive characteristics of HCC, providing a streamlined yet comprehensive approach to potentiate immunotherapy.",
  "abstract_shown": true,
  "affiliations": [
    "Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, the School of Pharmaceutical Sciences Guangzhou Medical University Guangzhou China",
    "GMU‐GIBH Joint School of Life Sciences Guangzhou Medical University Guangzhou China",
    "Department of Pathology, Yong Loo Lin School of Medicine National University of Singapore Singapore Singapore"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Chuyu Huang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yun Ye"
    },
    {
      "affs": [
        1
      ],
      "name": "Yi Guo"
    },
    {
      "affs": [
        1
      ],
      "name": "Guozheng Liao"
    },
    {
      "affs": [
        1
      ],
      "name": "Linyi Luo"
    },
    {
      "affs": [
        2
      ],
      "name": "Lingwen Ding"
    },
    {
      "affs": [
        0
      ],
      "name": "Yingling Miao"
    },
    {
      "affs": [
        0
      ],
      "name": "Linping Zhao"
    },
    {
      "affs": [
        1
      ],
      "name": "Yongchang Ouyang"
    },
    {
      "affs": [
        0
      ],
      "name": "Shiying Li"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0atchp6br98w6.bib",
  "cited_by": 0,
  "doi": "10.1002/exp2.70226",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13643016/",
  "id": "0atchp6br98w6",
  "issns": [
    "2766-8509",
    "2766-2098"
  ],
  "landing_url": "https://doi.org/10.1002/exp2.70226",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "2730|Cancer Immunotherapy and Biomarkers"
    ]
  ],
  "openalex": "W7220836803",
  "pdf_url": "https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/exp2.70226",
  "pmcid": "PMC13643016",
  "pmid": "42846631",
  "published": "2026-10-06",
  "publisher": "Wiley",
  "ris": "https://research.draconitic.com/paper/0atchp6br98w6.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T12:23:35Z",
      "native_id": "PMC13643016",
      "source": "pmc",
      "url": "https://doi.org/10.1002/exp2.70226"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cancer Immunotherapy and Biomarkers",
      "subfield": "oncology"
    }
  ],
  "title": "A PD‐L1 Nanobody‐Engineered Synthetic RNA Virus Enhances Hepatocellular Carcinoma Immunotherapy by Interfering PCSK9 and Upregulating MHC‐I",
  "title_text": "A PD‐L1 Nanobody‐Engineered Synthetic RNA Virus Enhances Hepatocellular Carcinoma Immunotherapy by Interfering PCSK9 and Upregulating MHC‐I",
  "type": "peer-reviewed",
  "updated_at": "2026-11-04T12:21:15Z",
  "url": "https://research.draconitic.com/paper/0atchp6br98w6",
  "venue": "Exploration",
  "versions": []
}