Nature: after removing the invisibility cloak! Leukemia stem cells have nowhere to hide. Immune cells are successfully hunted down!

July 22, 2019 / Biovalley / leukemic stem cells protect themselves from immune defense by inhibiting target molecules of killer cells, which can be deceived by drugs In the journal Nature, scientists from Basel, Tubingen and Heidelberg describe new treatments that could be derived from these results Patients with acute myeloid leukemia (AML) usually relapse after treatment The stem cells that survive the treatment of leukemia lead to the recurrence of the disease Scientists can partly explain this: stem cells have a protective mechanism that makes them resistant to chemotherapy But how do they escape immune defenses? Scientists from the University of Basel and the University of Tubingen, the German Cancer Research Center (DKFZ), the Heidelberg Institute of stem cell technology and Experimental Medicine (hi-stem) and the German Cancer Alliance (dktk) have investigated the phenomenon and found an amazing mechanism Photo source: Wikipedia researchers analyzed leukemic cells from 175 AML patients and found that leukemic stem cells inhibited nkg2d-l protein on their surface These proteins enable natural killer cells (NK cells) to recognize damaged and infected cells, as well as cancer cells, and kill them if necessary Therefore, these leukemia stem cells will not be damaged by the immune system On the other hand, leukemia cells without stem cell characteristics present these target molecules on their surface, so they are controlled by NK cells In mice transplanted with AML cells from patients, the researchers found that normal AML cells (without stem cell characteristics) were controlled by NK cells, while nkg2d-l negative leukemic stem cells escaped the killer's control Claudia lengerke, from the University of Basel hospital and the University of Basel, said: "the link between stem cell characteristics and the immune system's ability to escape has not been known until now "Helmut Salih, from the University Hospital of Tubingen and the German Cancer Society dktk, added:" in leukemia stem cells, the basic mechanism of this immune resistance is obviously to inhibit the dangerous signals on the cell surface, such as nkg2d-l "What is behind this extraordinary protection mechanism? Scientists note that leukemic stem cells produce particularly high levels of PARP1, an enzyme that blocks the production of nkg2d-l Preclinical experiments in mice that have been transfused with human leukemic cells have shown that PARP1 plays an important role in immune evasion: if drug treatment suppresses PARP1 in these animals, leukemic stem cells will again express nkg2d-l, which is then recognized and eliminated by NK cells Over the years, cancer treatment involving the immune system has been successfully applied to allogeneic stem cell transplantation in AML patients with certain diseases In recent years, new immunotherapy methods have been further developed and clinical trials are under way "Our results show how cancer stem cells cleverly trick the immune system "Andreas Trumpp of the German Cancer Research Centre and HI-STEM said These results provide a basis for the possibility of combining PARP inhibitors with active NK cells in the treatment of malignant leukemia stem cells The scientists involved are now planning to evaluate the method in a clinical study Reference: essence of NKG2D lives defines leukaemia stem cells and mediates their immune evaluation, nature (2019) Doi: 10.1038/s41586-019-1410-1