Scientists Identify Mechanism That Prevents the Immune System from Fighting Blood Disorders

Blocking this signal helped strengthen the immune response in laboratory experiments and showed promising results in an experimental disease model.

The discovery could pave the way for the development of new treatments for patients with certain genetic mutations.

The study, conducted by an international team led by Karl Landsteiner University of Health Sciences in Krems, Austria, focused on myeloproliferative neoplasms — chronic blood disorders in which the bone marrow produces excessive numbers of blood cells. These conditions can lead to blood clots, bone marrow scarring and the development of acute myeloid leukemia.

The researchers compared the activity of natural killer (NK) cells — immune cells that destroy abnormal and cancerous cells — in patients with CALR and JAK2 gene mutations. In patients with CALR mutations, these cells retained their ability to produce substances needed to eliminate abnormal cells. However, researchers found increased levels of the TIGIT receptor on their surface, which suppresses the immune response. At the same time, patients had elevated levels of a molecule called CD112, which can activate this receptor.

When the researchers blocked TIGIT using antibodies, natural killer cells became more effective at destroying abnormal cells under laboratory conditions. In an experimental disease model, the treatment also showed a trend toward reducing abnormally high platelet counts in the blood.

According to the authors, blocking TIGIT could become an additional treatment approach for patients with myeloproliferative neoplasms carrying CALR mutations. Unlike therapies that directly target mutated cells, this strategy is designed to help the body's own immune system control the disease more effectively.

The findings remain preliminary. Further research is needed to assess the method's effectiveness and safety before its potential for treating patients can be evaluated.