Researchers at National Taiwan University have developed a liver-directed IL-10 gene therapy that strengthens cancer-fighting immune cells and suppresses liver tumors in mice. The treatment also generated long-lasting immune memory cells that remained in the liver after tumors disappeared.
Hepatocellular carcinoma (HCC), the most common form of liver cancer, remains difficult to treat because the liver naturally suppresses immune responses. While this immune tolerance normally protects the liver from excessive inflammation, it also creates an environment where cancer cells can evade immune attack.
Researchers at National Taiwan University have developed a new liver-directed gene therapy approach designed to overcome this challenge. Their study demonstrates that delivering the immune-regulating molecule interleukin-10 (IL-10) directly to the liver can stimulate strong antitumor immune responses and suppress liver tumor growth in mice.
The study is published in the Journal for ImmunoTherapy of Cancer.
The team used an adeno-associated virus (AAV) vector to transport the IL-10 gene specifically into the liver. Unlike repeated injections of recombinant proteins, AAV-based gene delivery allows sustained local production of IL-10 within liver tissue.
The researchers found that this localized treatment significantly reduced tumor burden in multiple mouse models of liver cancer.
Further investigation revealed that the therapy reshaped the immune environment inside liver tumors. Mice treated with AAV-IL-10 showed increased infiltration of CD8+ T cells, which are key immune cells responsible for killing cancer cells.
These T cells also displayed stronger functional activity, including increased production of interferon-gamma and granzyme B, two molecules involved in destroying tumor cells.
Importantly, the researchers discovered that the therapy promoted the development of tissue-resident memory-like CD8+ T cells in the liver. These long-lived immune cells remained in liver tissue even after tumors were eliminated, suggesting the possibility of durable immune protection against cancer recurrence.
The study also showed that the antitumor effects were mainly confined to the liver, highlighting the importance of local immune modulation within the liver microenvironment. This organ-specific immune activation may help reduce unwanted systemic immune effects.
The researchers believe that liver-directed IL-10 therapy could provide a new strategy for improving immunotherapy outcomes in liver cancer. The findings may also help guide future approaches for treating other cancers that develop in highly immunosuppressive environments.
"Our study demonstrates that targeted delivery of IL-10 can reshape the liver immune environment and enhance the body's ability to fight liver cancer," says corresponding author Dr. Ya-Hui Chuang, professor of clinical laboratory sciences and medical biotechnology at National Taiwan University.
Publication details
Chia-I Lin et al, Liver-directed AAV-IL-10 therapy enhances CD8+T cell-mediated immunity against hepatocellular carcinoma, Journal for ImmunoTherapy of Cancer (2026). DOI: 10.1136/jitc-2025-012460
Journal information: Journal for ImmunoTherapy of Cancer
Key medical concepts
Carcinoma, Hepatocellular
CD8-Positive T-Lymphocytes
Clinical categories
Oncology
Provided by National Taiwan University