Deciphering the Interplay of Regulatory T Cells in the Regulation of Myeloid Leukemia Stem Cells
Leukemia stem cells (LSCs) are the origin of any myeloid leukemia and are thought to reside at the top of the leukemic hierarchy, like hematopoietic stem cells (HSCs) in hematopoiesis. LSCs are often resistant against standard treatment and against immune control due to various escape mechanisms and therefore represent a major obstacle for the cure of leukemia. This resistance is partially mediated by protective mechanisms of the HSC niche including immune cells in the bone marrow (BM) in which these LSCs reside. In leukemia, the BM microenvironment changes dramatically inter alia with regulatory T cells (Tregs) accumulating. However, little is known about the mechanisms that regulate these changes in the BM and lead to an immunosuppressive environment. The aim of this proposal is to determine the as yet unanticipated role of Tregs on LSCs, and thereby identify novel immunotherapeutic mechanisms to re-direct the body’s immune system against LSCs. As the gut flora critically regulates Treg development, we hypothesize that Tregs fuel an immunosuppressive environment contributing to LSC survival and that the gut flora is an important driver of Treg imbalance in leukemia (funded by the Swiss National Science Foundation).
