The immune system is complex and detailed understanding of its mechanisms still missing. Only a precise interaction of various factors ensures reliable and correct immune response in a healthy body. Unregulated immune response is a major cause of many diseases such as cancer, autoimmunity and immunodeficiency.

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In the new study, published in the «Blood» journal, the researchers looked at the state of the four patients with malignant tumors, autoimmune conditions and immunosuppression. All four patients had germline mutations in the gene encoding CD137, which led to the co-receptor-protein dysfunction CD137.Eta dysfunction violates the most important factors immune surveillance, in particular for the prevention of viral infections and the development of lymphoma associated with infection Epstein-Barr virus (EBV).

"We not only found a new syndrome of predisposition to tumors, especially children's lymphoma, but also learned more about the basic functions of CD137 in Immunity" - the researchers reported.

The mechanism of the disease in detail:

Co-receptors play a fundamental role in the regulation and fine tuning the signal strength of so-called antigen receptors that help the immune cells to recognize foreign bodies. Impaired function of these immune receptors may lead to increased susceptibility to infections, autoimmune disorders and cancer. CD137 or a 4-1BB costimulatory molecule, which is often expressed on activated T cells to ensure proper function of T-cells. Recent studies have also examined CD137 as a "target" for cancer immunotherapy.

EBV - this is the herpes virus, which infects more than 90% of all people and remains dormant in the body forever. In people with T-cell EBV infection impaired function may lead to lymphoproliferative disorders until the development of malignant lymphoma.

"As a biologist and a graduate student in the lab, it is interesting to observe how we overcome the gap from a deep understanding of the genetic analysis to the impaired immune response, in particular, viral infection EBV» - said one of the researchers.

Diseases caused by a single gene defect, eg, CD137, provide a unique opportunity to study the effects of such errors for the whole organism. Thus, we can get a mechanistic understanding of the paths the signals required for reliable immune surveillance in the body of the EBV.

The study demonstrated the key role of CD137 in the control of EBV virus the immune system. If the body can not keep the virus under control, it can lead to the development of lymphoma.

The scientists hope that their findings will help in the development of new targeted therapies that can stop this dangerous cancer development.

Date of publication: 
Thursday, September 19, 2019