Acute myeloid leukaemia 'invisible' to the immune system

Australian researchers have discovered how a highly aggressive type of blood cancer, known as acute myeloid leukaemia (AML), can ‘switch off’ a protein known as MHC class II, causing the leukaemia to become invisible to the immune system. Described in the journal Cancer Cell, this molecular switch allows cancer cells to evade recognition and prevents the immune system from destroying them.

Senior author Associate Professor Marian Burr, from The Australian National University (ANU), said until now it was unknown how the leukaemia cells were able to switch off MHC class II and evade immune detection. To investigate this, the scientists mimicked the growth of the aggressive AML cells in humans by growing them in the lab.

“Using cutting-edge CRISPR gene editing technology, we were able to identify that a specific group of proteins, called the CtBP complex, were responsible for switching off MHC class II in AML and other cancers,” Burr said.

The good news, according to the researchers, is that drugs targeting this molecular switch could be used to turn MHC class II back on again. By restoring MHC class II to the surface of the AML cells, the cancer is once again visible to the immune system and can be detected and eliminated.

“We found that inhibiting the CtBP complex using specific drugs restored MHC class II levels and enhanced the ability of immune system cells to destroy the tumour cells,” Burr said.

Senior author Professor Mark Dawson, from the Peter MacCallum Cancer Centre, said, “This discovery reveals a potential new approach to treat patients who have relapsed after having a bone marrow transplant.

“Specific inhibitors of the CtBP complex are widely available, although further research is needed to ensure they are safe for human trials and that our preclinical findings translate into meaningful improvements in patient outcomes.”

Burr said the findings could also help treat patients with a range of other cancers, stating “Cancer immunotherapies have been extremely effective in many different types of cancer, although treatment resistance remains a fundamental issue for some patients.

“We hope that this work will help to improve the effectiveness of immunotherapy, especially for aggressive types of cancers.”

Image credit: iStock.com/OGphoto

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