Blocking gene boosts T-cell attacks on chronic hepatitis B virus and tumors

Researchers from the Institute of Microbiology at the Chinese Academy of Sciences and their colleagues in Beijing have discovered that the gene ANKRD11 plays a crucial role in weakening the immune response of CD8+ T cells during chronic hepatitis B virus (HBV) infection and cancer. This finding was published in Nature Immunology on September 11.

HBV affects approximately 296 million individuals worldwide and is a major cause of severe liver diseases. A significant obstacle in controlling chronic HBV is the weakened state of CD8+ T cells, which makes it difficult for them to multiply and effectively target infected cells. To address this issue, the research team designed a mouse model that replicates human immune responses to HBV and discovered that ANKRD11 acts as a suppressor of the AP-1 signaling pathway, which typically strengthens CD8+ T cell reactions against infections and tumors.

By eliminating ANKRD11 specifically in T cells, the researchers observed an improvement in the immune cells' ability to combat infection and cancer, as they generated higher levels of essential immune molecules and demonstrated increased effectiveness in attacking infected and cancerous cells. The research also revealed that ANKRD11-deficient T cells displayed a stronger resistance to immune response suppression.

In several disease models, mice with HBV, cancer or other viral infections experienced more active immune cells in the liver, better virus clearance and improved disease outcomes when ANKRD11 was absent in their T cells. Furthermore, combining this approach with existing therapies demonstrated enhanced outcomes. The study identifies ANKRD11 as a significant regulator that dampens T cell responses to chronic viral infections and cancer.

Targeting ANKRD11 could potentially bolster the body's own immune response to chronic HBV infection and cancer, especially in situations where existing treatments are ineffective.