Multiple myeloma is a type of bone marrow cancer that mainly affects people over the age of 60 and in many cases cannot be cured. Researchers at the University Hospital of the Friedrich-Alexander University Erlangen-Nuremberg (German acronym: FAU) have now found a new approach for a possible therapy of this cancer. The research results have now been published in the scientific journal "Immunity".
Multiple myeloma develops when a certain type of white blood cell, known as B cells, multiplies uncontrollably in the blood. As a result, bones are destroyed and patients also suffer from anemia, chronic infections and kidney problems. Although several effective chemotherapies are available, about one third of those affected do not respond to the available treatments. Even if treatment is effective, the tumor is not cured but may eventually return. It was already known that the macrophage cells of the immune system, which are actually important for fighting off invaders in the body, work for the tumor in multiple myeloma. They support inflammation and thus promote the survival of the tumor and its growth.
The study by the FAU research team, led by PD Dr. Heiko Bruns of the Department of Medicine 5 for Hematology and Internal Oncology (Erlangen, Germany) in cooperation with scientists from Milan, has now discovered what happens at the molecular level when the macrophage cells release inflammatory signals in the bone marrow. A blood component called beta-2-microglobulin seems to play an important role in this process. This is because the more severely the bone cancer has affected the body, the more of this protein that is detectable in the patients' blood.
The Erlangen team has discovered that this is not just a side effect of the disease, but that this protein causes the phagocytes to make the disease worse. This is because the protein is devoured by the phagocytes - but not digested and broken down. In a sense, it weighs heavily on the stomach of the phagocytes, causing them to send out inflammatory signals that in turn benefit the tumor and its harmful effects in the body. The research team was able to demonstrate that cancer can be significantly mitigated if it is possible to block these inflammatory signals.
Dr. Heiko Bruns added that "phagocytes, macrophages, are essential cells to defend our organism against tumor development. Many tumors can break through this line of defense because they manage to evade macrophage activity. We have seen that multiple myeloma employs an even more subtle strategy: It plays macrophage activity to its own advantage. Understanding how multiple myeloma achieves this is extremely relevant. Targeted blockade of the inflammasome may provide a new adjuvant therapy strategy for patients in the future."
Heiko Bruns, Daniel Hofbauer, Dimitrios Mougiakakos et. al: β2-microglobulin triggers NLRP3 inflammasome activation in tumor-associated macrophages to promote multiple myeloma progression. Immunity, 20 July, 2021.