{
  "abstract": "Background The liver’s inherently immunosuppressive microenvironment presents a major barrier to effective immunotherapy for hepatocellular carcinoma (HCC). Although interleukin-10 (IL-10) has demonstrated antitumor activity in several cancer models, its therapeutic potential in HCC remains unclear. Here, we investigated whether liver-directed delivery of IL-10 using an adeno-associated virus vector (AAV-IL-10) could enhance antitumor immunity in HCC.Methods Syngeneic orthotopic and intrahepatic metastatic HCC mouse models were used to evaluate the effects of liver-directed AAV-IL-10 therapy. Tumor burden, immune cell infiltration, and functional activation were assessed by flow cytometry and related analyses.Results Liver-directed AAV-IL-10 treatment significantly reduced intrahepatic tumor burden and promoted robust infiltration of CD8 + T cells into the tumor microenvironment. AAV-IL-10 enhanced the functional activation of natural killer cells and CD8+ T cells, as reflected by increased expression of effector cytokines and cytotoxic molecules. Notably, AAV-IL-10 augmented the effector capacity of terminally exhausted CD8+ tumor-infiltrating lymphocytes and expanded a population of CD8+ T cells with a tissue-resident memory (Trm)-like phenotype. These Trm-like CD8+ T cells were liver-resident and persisted after tumor clearance. Importantly, the antitumor effects of AAV-IL-10 were confined to the liver and did not affect the growth of distant subcutaneous tumors.Conclusions Liver-directed AAV-IL-10 delivery overcomes local immunosuppression and enhances CD8 + T cell-mediated antitumor immunity in murine HCC models. These findings support targeted IL-10 delivery as a promising strategy to improve immunotherapy outcomes in liver cancer.",
  "authors": [
    {
      "affiliations": [
        "Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei, Taiwan"
      ],
      "name": "Chia-I Lin"
    },
    {
      "affiliations": [
        "Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei, Taiwan"
      ],
      "name": "Yi-Wei Chiu"
    },
    {
      "affiliations": [
        "Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei, Taiwan"
      ],
      "name": "Meng-Syuan Yen"
    },
    {
      "affiliations": [
        "Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei, Taiwan"
      ],
      "name": "Yu-Wen Wang"
    },
    {
      "affiliations": [
        "Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei, Taiwan"
      ],
      "name": "Ying-Hsuan Wu"
    },
    {
      "affiliations": [
        "Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University, Taipei, Taiwan",
        "Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan"
      ],
      "name": "Ya-Hui Chuang"
    }
  ],
  "title": "Liver-directed AAV-IL-10 therapy enhances CD8+ T cell-mediated immunity against hepatocellular carcinoma",
  "uid": "b5f527ca-6ed3-5c55-a827-f95a1ec89be0"
}