Dominik Böhm

Name: Dominik Böhm

Nationality: German

Academic Background: BSc in Chemistry and Biochemistry, LMU Munich, MSc in Biochemistry, LMU Munich

Project Title: T cell-based immuno-oncological targeting of acute myeloid leukemia

Project Background:  Our bodies possess a defense system that recognizes and eradicates cells and substances that are different from our own and could be harmful to us; the immune system. The immune cells, and in particular a class of immune cells called T cells, can also recognize cancer cells as something foreign that should be removed. This mechanism is used in cancer immunotherapy. However, since the immune cells will try to get rid of them, cancers evolve as they develop to keep the immune system in check and the immune cells cannot target them. This so-called immunosuppression is also one of the main obstacles in making immunotherapy effective in acute myeloid leukemia (AML), an aggressive cancer of the myeloid blood cells. The problem is that we don’t yet understand the mechanisms that AML cells use to control the T cells and other immune cells. There are different possible ways of how AML cells may suppress T cells based on reported cell compositions in AML patient samples. On one hand, the AML cells may directly send signals to the T cells in order to “turn them off”. On the other hand, the AML cells may send signals to boost other normal immunosuppressive cells that are used by our body to regulate immune responses, such as regulatory T cells or immunosuppressive macrophages, and thereby turning off the immune response. If we can identify mechanisms to free the T cells from the cancer’s control, this can provide us with a very powerful tool to fight the cancer and prevent it from recurring.

Project Aim: In my project I am aiming to identify mechanisms by which we can release T cells to eradicate AML cells. I am doing this pursuing two approaches. One aim will be to find drugs that relieve the immunosuppression in AML and reactivate the T cells using high throughput screens. Deep profiling of AML patient samples will elucidate which mechanisms the hit drugs target and which cell populations are affected. However, even though AML cells are very effective at suppressing T cells, there are small subpopulations of T cells that still can recognize and kill the AML cells. Therefore, I am aiming to characterize these T cell subpopulations in order to learn what they actually recognize, when they get activated and kill the AML cells.

Expected Outcome:  The results of this study will give an insight into the key immunosuppressive factors in AML and how they can be targeted to enable an effective immune response. Furthermore, I hope to learn what AML-targeting T cells recognize on the AML cells to induce an immune response. This information could be used to boost these AML-targeting immune cells, for example through immunization approaches. Taken together, these studies may provide key information for developing new immunotherapies against AML and thereby improving the outcome for patients suffering from this very aggressive cancer.

Contact: dominik.bohm@bric.ku.dk