AML is a form of leukemia that originates in the bone marrow. The leukemia cells spread through the body via the blood. This form of leukemia is diagnosed in about 25 children each year. Thanks in part to scientific research, the chance of survival is now 80%. To achieve a cure for every child with AML with optimal quality of life, research into new treatments remains important.
Immunotherapy
Immunotherapy is a promising new form of treatment. It strengthens the immune system so that it can recognize and destroy cancer cells. Development of immunotherapies to treat AML is currently in its infancy.
To develop an effective form of immunotherapy for these children, it is important to understand how leukemia cells in the bone marrow escape the immune system. Several scientists are investigating this tumor microenvironment. However, little attention has been paid to the spatial organization of immune and leukemia cells in the bone marrow.
Joost Koedijk, PhD candidate in the Heidenreich and Zwaan groups, has mapped this for the first time for children with AML. For this he collaborated with researchers from Máxima, the Dana-Farber Cancer Institute in Boston and Aarhus Hospital from Denmark. The results of the study, which was co-sponsored by KiKa, were published in Leukemia.
Presence of immune cells and response
Koedijk and his colleagues examined bone marrow biopsies of children with AML from the biobank of the Máxima and others. 'We found that almost one third of the children have many immune cells, such as T and B cells, in the bone marrow. This offers perspective for the development of immunotherapy. Because these cells occur in groups and may be able to create a new immune response. This is similar to what has been seen in previous research in solid tumors.' At the same time, two-thirds of children with AML have few or no T- and B-cells in the bone marrow, indicating that a different form of immunotherapy is needed for them. Koedijk and his colleagues are investigating this further.
This study used bone marrow biopsies instead of bone marrow fluid. This allowed the researchers to identify exactly where the immune cells were located. 'This keeps the spatial organization of the tissue intact, allowing you to see features that are lost when bone marrow fluid is aspirated.'
Next steps
Now that more is known about the tumor microenvironment in the bone marrow of children with AML, researchers can use this information to take next steps in finding an effective immunotherapy to treat children with AML.
Prof. Dr. Olaf Heidenreich, last author and principal investigator together with Prof. Dr. Michel Zwaan, said: ‘In particular, researchers in the field of T-cell-targeted immunotherapies such as bispecific antibodies and T-cell receptor immunotherapies can benefit greatly from these new insights. In addition to wanting to understand much more about how immune cells and leukemia cells communicate with each other in the bone marrow, we are now also looking for what is the most ideal time to use immunotherapy and whether it can be combined with novel targeted therapies such as menin inhibitors. For example, is there more effect before or just after treatment with chemotherapy?’
Zwaan also sees opportunities to use the lessons learned to map the tumor microenvironment of other childhood cancers. 'Because all Dutch research into childhood cancer is centralized at the Máxima, we can relatively easy increase the impact of our research. For example, with this research we are not only helping children with AML, but we may also be able to provide new insights within immunological research in solid tumors, such as bone and brain tumors.'