Scientists identify protein that aids in cancer relapse

Cancer stem cells that lack expression of NKG2D-L on their surface survive chemotherapy as well as escape the body's immune defence 

By DTE Staff
Published: Thursday 18 July 2019
Photo: Schürch/Lengerke, University and University Hospital of Basel__

Scientists have identified a protein that hides acute myeloid leukemia (AML) stem cells from the body's immune system, boosting their chances of relapse even after a successful treatment, according to a new study.

AML is a type of blood and bone marrow cancer, which progresses rapidly as myeloid cells affect the production of normal white blood cells, red blood cells and platelets. Treatments, which include chemotherapy, other drug therapy and stem-cell transplants help in remission.  

AML cells that lack expression of protein, called NKG2D-L, on their surface survive chemotherapy as well as escape the body's immune defence or natural killer (NK) cells, found the study published in the journal Nature.

To understand, a team of scientists analysed the leukemia cells of 177 AML patients and transferred both leukemia cells and NK cells into mice.

They found that the NKG2D-L-negative leukemia stem cells escaped NK cells, while these immune cells could control AML cells without stem cell properties.

“Such a connection between stem cell properties and the ability to escape the immune system was unknown until now,” Claudia Lengerke from the University Hospital of Basel, said in a release.

“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.

However, this protective mechanism can be tricked with drugs, according to the researchers.

Experiments on mice showed that leukemia stem cells escape the immune defense because of PARP1 — an enzyme that blocks the production of NKG2D-L.

Mice treated with drugs that inhibit PARP1 induced NKG2D-L into cancer stem cells making them visible to the immune system. Once recognised the NK cells eliminated them.

“Our results show how cancer stem cells cleverly trick the immune system. The elucidation of the underlying mechanism now makes it possible to counterattack,” said Andreas Trumpp, German Cancer Research Center and HI-STEM.

Combining PARP inhibitors with active NK cells can help treat malignant leukemia stem cells, the researchers said, adding the need to evaluate the approach in a clinical study.

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