Patients with acute myeloid leukemia (AML) often relapse after apparently successful treatment.
Patients with acute myeloid leukemia (AML) often relapse after apparently successful treatment. Leukemia stem cells that survive the therapy are responsible for the return of the disease. Scientists can partially explain this phenomenon: The stem cells have protective mechanisms that make them resistant to chemotherapy. But how do they manage to escape the immune defense?
A team of scientists from the University Hospitals of Basel and Tübingen, the German Cancer Research Center (DKFZ), the Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM)* and the German Cancer Consortium (DKTK) have now investigated this phenomenon and discovered a surprising mechanism.
The researchers analyzed the leukemia cells of 177 AML patients and found that the cancer stem cells lack expression of NKG2D-L proteins on their surface. These proteins enable the natural killer cells (NK cells) to recognize and kill damaged and infected cells as well as cancer cells. By suppressing NKG2D-L, the leukemia stem cells escape destruction by the immune system. Leukemia cells without stem cell properties, on the other hand, present these target molecules on their surface and can therefore be targeted by NK cells.
Using mice to which AML cells from patients had been transferred, the researchers showed that only AML cells without stem cell properties were controlled by the NK cells, while the NKG2D-L-negative leukemia stem cells escaped the killer squad. "Such a connection between stem cell properties and the ability to escape the immune system was unknown until now," said Claudia Lengerke from the University Hospital of Basel and the University of Basel. "An essential mechanism of this immune resistance in leukemia stem cells is apparently the suppression of danger signals such as NKG2D-L on the cell surface," added Helmut Salih from the University Hospital of Tübingen and the German Cancer Consortium DKTK.
Read more at: German Cancer Research Center
NK cells (red) attack normal leukemia cells (green). Leukemia stem cells (blue), on the other hand, suppress NKG2DL expression at their surface and thus escape destruction by the immune system.
(Photo Credit: © Schürch/Lengerke, University and University Hospital of Basel)