Acute myeloid leukemia stem cells elude the body’s immune cells by deactivating a danger detector. The underlying mechanisms and the potential new therapeutic approaches that this gives rise to have been detailed in the journal Nature by researchers from the University of Basel and University Hospital Basel in collaboration with colleagues in Germany.
Patients treated for acute myeloid leukemia (AML) often achieve remission but then later experience relapses due to surviving subpopulations of leukemia stem cells. The researchers report that these leukemia stem cells or cancer stem cells are not only more resistant to chemotherapies, but can also selectively evade destruction by immune cells: although they exhibit the same cancer-specific genetic mutations as other cancer cells of the same patient, leukemic stem cells have additional stem cell-specific mechanisms of immune defense, which they use to ensure their survival.
Immune evasion using an enzyme
For example, the cancer stem cells suppress the surface expression of ligands of the danger detector NKG2D in order to evade natural killer cells. This specific mechanism of immune evasion is mediated by the formation of the enzyme PARP1 in the cancer stem cells, as the researchers report.
Treatment with PARP1 inhibitors can induce NKG2D ligands on cancer stem cells, and pre-clinical trials on mice have shown that immune cells can eliminate cancer stem cells following treatments of this kind.
Cancer therapies incorporating the immune system have been applied successfully for many years in the form of allogeneic stem-cell transplants to patients with leukemia in certain disease situations. In recent years, further immunotherapeutic approaches have been developed for leukemia as well as other cancers.
“However, our results indicate that – as with chemotherapy – cancer stem cells are also better at surviving immune attacks,” says study leader Professor Claudia Lengerke. The effectiveness of immunotherapies could therefore be improved if they were used in combination with treatments that sensitize cancer stem cells to immunological attack.
The study was conducted by the teams led by Professor Claudia Lengerke (Department of Biomedicine and Department of Hematology at the University of Basel and University Hospital Basel), Professor Helmut Salih (German Cancer Consortium Heidelberg, partner site Tübingen) and Professor Andreas Trumpp (University of Heidelberg and German Cancer Research Center, Heidelberg), in collaboration with other scientists.
Prof. Dr. Claudia Lengerke, Department of Biomedicine, University Hospital and University of Basel, Tel. +41 61 265 23 81, E-Mail: email@example.com
Anna M. Paczulla, Kathrin Rothfelder, Simon Raffel et al.
Absence of NKG2D ligands defines leukaemia stem cells and mediates their immune evasion
Nature (17 July 2019), doi: 10.1038/s41586-019-1410-1
Christoph Dieffenbacher | Universität Basel
Numbers count in the genetics of moles and melanomas
16.08.2019 | University of Queensland
Working out why plants get sick
16.08.2019 | Institut für Pflanzenbiochemie
Soft robots have a distinct advantage over their rigid forebears: they can adapt to complex environments, handle fragile objects and interact safely with humans. Made from silicone, rubber or other stretchable polymers, they are ideal for use in rehabilitation exoskeletons and robotic clothing. Soft bio-inspired robots could one day be deployed to explore remote or dangerous environments.
Most soft robots are actuated by rigid, noisy pumps that push fluids into the machines' moving parts. Because they are connected to these bulky pumps by tubes,...
Researchers at TU Graz are working together with European partners on new possibilities of measuring vehicle emissions.
Today, air pollution is one of the biggest challenges facing European cities. As part of the Horizon 2020 research project CARES (City Air Remote Emission...
Over the next three years, researchers from the Vrije Universiteit Brussel, University of Cambridge, École Supérieure de Physique et de Chimie Industrielles de la ville de Paris (ESPCI-Paris) and Empa will be working together with the Dutch Polymer manufacturer SupraPolix on the next generation of robots: (soft) robots that ‘feel pain’ and heal themselves. The partners can count on 3 million Euro in support from the European Commission.
Soon robots will not only be found in factories and laboratories, but will be assisting us in our immediate environment. They will help us in the household, to...
Scientists at the University of Leeds have created a new form of gold which is just two atoms thick - the thinnest unsupported gold ever created.
The researchers measured the thickness of the gold to be 0.47 nanometres - that is one million times thinner than a human finger nail. The material is regarded...
An international team of scientists involving the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) in Hamburg has unraveled the light-induced electron-localization dynamics in transition metals at the attosecond timescale. The team investigated for the first time the many-body electron dynamics in transition metals before thermalization sets in. Their work has now appeared in Nature Physics.
The researchers from ETH Zurich (Switzerland), the MPSD (Germany), the Center for Computational Sciences of University of Tsukuba (Japan) and the Center for...
16.08.2019 | Event News
14.08.2019 | Event News
12.08.2019 | Event News
16.08.2019 | Life Sciences
16.08.2019 | Physics and Astronomy
16.08.2019 | Medical Engineering