Acute myeloid leukaemia (AML) is a life-threatening form of blood cancer caused by the unchecked growth of immature bone marrow cells. The standard procedure for treating AML is the transplantation of allogeneic stem cells, in which bone marrow or blood stem cells from another person are transferred to the patient. With these cells, a new immune system develops in the body of the sick person that targets any remaining malignant leukaemia cells. This is known as the immune effect. “Unfortunately, even after stem cell transplantation, relapses can occur, which are frequently accompanied by a poor prognosis. After the transplantation, the newly donated immune system is in a position to control the leukaemia. In later stages, the disease often develops strategies to avoid immune system detection,” explains Christoph Schmid. “This phenomenon is called immune escape.”

Schmid holds a research professorship for transplantation and cell therapy at the Faculty of Medicine at the University of Augsburg. Together with Tatjana Sauerer, a cell biologist, and colleague Giuliano Filippini Velázquez from II. Medical Clinic at Augsburg University Hospital, he provides a comprehensive description of immune escape in their recently published article in the internationally renowned journal Molecular Cancer.

What causes immune escape?

Leukaemia cells use various strategies to evade control of the immune system. For example, they can change their surface proteins so that they are no longer recognised by the immune system, or they can slow down the reaction of the immune cells. Another strategy is the secretion of messenger substances that have a dampening effect on the immune system or impair the metabolism of the immune cells. Leukaemia cells can also shed entire parts of their genetic material, thus preventing the immune system from being able to develop recognition characteristics.

Customised treatment strategies

In their article, the authors explain the extent to which knowledge of these immune escape mechanisms is already being used to develop customised treatment strategies in the event of a relapse. However, this is currently only in use in clinical trials, as research is still in its infancy. “There are however a great number of known mechanisms that offer a good starting point for targeted interventions, but we need to increase our understanding in order to optimise the therapies. That’s why we have also provided an outlook on how new technologies can contribute to improving therapy for these patients, highlighting future treatment options,” explains Schmid. An example of a possible future therapy is the prescription of antibodies that neutralise inhibitory surface proteins. Medications that restore the metabolism of immune cells or that stimulate the entire immune system are also conceivable. Medications that cause the genes responsible for the formation of the immune system recognition structures to be “switched on” could also be a possible approach.

About the article

• Title: “Relapse of acute myeloid leukaemia after allogeneic stem cell transplantation: immune escape mechanisms and current implications for therapy”
• Authors: Dr. rer. nat. Tatjana Sauerer1, Giuliano Filippini Velázquez1, Prof. Dr. Christoph Schmid2 (1: First author, 2: Corresponding author)
• https://doi.org/10.1186/s12943-023-01889-6