ANKRD11 restrains CD8+ T cells in hepatitis B and cancer models

Researchers have identified ANKRD11 as a regulator that restrains CD8+ T-cell responses in experimental models of chronic hepatitis B virus infection and cancer. A team led by Zhou Xuyu of the Institute of Microbiology at the Chinese Academy of Sciences, with collaborators from Beijing Ditan Hospital and Capital Medical University, reported that the protein limits the activity of these infection-fighting immune cells by suppressing the AP-1 signaling pathway. The peer-reviewed study, published in Nature Immunology on September 11, found that removing ANKRD11 from T cells enhanced their capacity to respond to infected and cancerous cells in mice.

The work used a mouse model designed to reproduce key features of human immune responses to HBV. Chronic HBV infection affects an estimated 296 million people worldwide and can lead to serious liver disease, including cirrhosis and liver cancer. In the study’s model, CD8+ T cells normally weaken during persistent infection, multiply less effectively and become less able to attack virus-infected cells. The researchers combined whole-genome genetic screening with functional experiments to identify genes that could influence T-cell responses during chronic infection. Ankrd11 was selected for further study because it emerged as a strong candidate and had not previously been characterized as a regulator of this response.

Deleting Ankrd11 specifically in T cells did not measurably impair their development, but it substantially increased their antiviral and antitumor activity. The altered cells produced higher levels of key immune molecules and attacked infected and cancerous cells more effectively. Gene-expression analysis indicated that pathways associated with T-cell function were more readily activated when ANKRD11 was absent. The researchers also found that ANKRD11-deficient T cells were more resistant to signals that normally dampen immune responses. Together, these observations support the conclusion that ANKRD11 acts as a molecular brake on CD8+ T-cell activity, with AP-1 signaling among the pathways restrained by the protein.

In HBV-infected mice, selective removal of Ankrd11 from T cells resulted in more active immune cells within the liver, improved viral clearance and better disease outcomes. Separate experiments in another viral infection model and a cancer model showed that T cells lacking Ankrd11 could better control infection and shrink tumors, including in settings where other treatments had failed. Combining the approach with existing therapies produced a stronger effect in the researchers’ experiments. These findings provide preclinical evidence that targeting ANKRD11 may help restore immune activity in chronic infection and cancer, but the work was conducted in mouse models and does not establish safety or effectiveness in people. Any therapeutic use would require additional studies and clinical evaluation.

Subject of Research: Experimental evidence that ANKRD11 suppresses CD8+ T-cell responses in mouse models of chronic hepatitis B virus infection and cancer

Article Title: Researchers identify ANKRD11 as a brake on T-cell responses to chronic hepatitis B virus and cancer

Article References: Researchers identify ANKRD11 as a brake on T-cell responses to chronic hepatitis B virus and cancer. Original publication (Bibliographic details unavailable.)

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Keywords: ANKRD11, CD8+ T cells, hepatitis B virus, AP-1 signaling, antiviral immunity, cancer immunology, mouse models, immune evasion, Researchers, identify, brake, T-cell