Fighting chronic hepatitis B virus (HBV) and cancer is difficult because certain immune cells, called CD8⁺ T cells, become less effective over time. A research team led by Prof. ZHOU Xuyu at the Institute of Microbiology of Chinese Academy of Sciences, along with the team of Beijing Ditan Hospital and Capital Medical University, discovered that a protein called ANKRD11 plays an important role in reducing these immune cells’ activity. The scientists also found that ANKRD11 works by blocking a pathway (AP-1) that usually helps these cells fight infections and tumors. This important study was published in Nature Immunology on September 11, 2026.

HBV infects about 296 million people worldwide and is a leading cause of serious liver diseases like cirrhosis and liver cancer. One major reason the immune system struggles to control chronic HBV is that CD8⁺ T cells, which normally attack infected cells, lose their strength and can't multiply well. In chronic HBV, this problem is made worse by the unique environment of the liver, which weakens immune responses. As a result, some current treatments that boost the immune system do not work well for HBV. There is a strong need to find new ways to help the immune system fight this infection.

Previously, the research team created a special mouse model that could mimic how humans fight HBV. They found a key target of the immune response in these mice. In their new study, they used advanced genetic tools to look across the whole genome and identify genes that might affect how T cells respond to chronic HBV. Out of many possible genes, they focused on Ankrd11 because it was new, showed strong results, and made sense as a regulator of how genes are turned on or off in immune cells.

When the scientists removed Ankrd11 from T cells in mice, it did not affect how these cells developed, but it made them much stronger at fighting infections. These T cells produced more important immune molecules and could better attack infected or cancerous cells. On a deeper level, the team found that without ANKRD11, the genes that help T cells work properly were turned on, showing that ANKRD11 acts like a brake, keeping these immune cells from becoming too active. In addition, T cells without ANKRD11 could resist signals that normally weaken the immune system.

The team tested their findings in several disease models. In mice with HBV, removing Ankrd11 from T cells led to more active immune cells in the liver, helped clear the virus, and improved disease outcomes. In another virus model and in a cancer model, T cells without Ankrd11 could better fight the virus and shrink tumors—even in cases where other treatments had failed. The researchers also found that combining this approach with existing therapies made the treatment even stronger.

This research reveals that ANKRD11 is an important protein that holds back the immune system's ability to fight viruses and cancer. Targeting ANKRD11 could lead to new treatments for chronic HBV and cancer by boosting the body's own immune response, especially in cases where current therapies are not enough.

Figure: Proposed dynamics of antigen-specific CD8⁺ T cell populations regulated by Ankrd11 in chronic infection and cancer (Image by Prof. ZHOU Xuyu ’s group)

Full text link: Ankrd11 Deficiency Reprograms CD8+ T Cell Differentiation to Enhance Immunity in Chronic Infection and Cancer