April 30, 2020

Research brings new knowledge of Graft-versus-host disease mechanisms

Improved understanding may help prevent rejection of blood stem cell transplants in cancer patients.

Graft-versus-host disease (GVHD) is a potentially life-threatening complication of blood stem cell transplants, a therapy for blood cancers. Blood cancers such as leukaemia, lymphoma and myeloma, are cancers of the immune system and are common in both children and adults.

Like most cancers, blood cancers are usually treated using chemotherapy or radiotherapy, but when these therapies aren’t successful, blood stem cell transplants are attempted.

This transplant therapy seeks to replace the patient’s diseased bone marrow, with healthy cells from a matching donor to generate new, cancer-free bone marrow and a working immune system.

In a paper published recently in Immunology and Cell Biology, scientists Dr Nicholas Geraghty, Dr Debbie Watson and Professor Ronald Sluyter, from the Illawarra Health and Medical Research Institute and the University of Wollongong School of Chemistry and Molecular Bioscience, examine what causes the transferred stem cells to reject the host.

When blood from healthy donors is transplanted into a patient, in some cases the transplanted immune cells recognise the host cells as foreign causing them to attack healthy tissues, which leads to GVHD.

Professor Sluyter, Dr Watson and Dr Geraghty have taken a closer look at the mechanism of GVHD to determine why the damaged host cells release a molecule called adenosine triphosphate (ATP).

“So in GVHD, instead of the body rejecting the transplant, the transplant rejects the body. As part of the disease, the damaged “host” cells release an immune molecule, called (ATP), which can activate the “graft” immune cells to promote inflammation and damage the recipient’s tissues such as the liver, gut and skin,” Dr Geraghty said.

Adenosine triphosphate (ATP) is an organic compound that is often called the “energy currency of the cell”. Every cell uses ATP for energy.

“This recent publication, along with previous studies, suggests that the ATP activates a molecule on immune cells called P2X7 which promotes GVHD. Therapies that can block P2X7 may limit or prevent GVHD in people with blood cancer after stem cell transplants,” Dr Geraghty added.

The International Day of Immunology is celebrated each year on 29 April, and is dedicated to increasing global awareness of the importance of immunology in the fight against infection, autoimmunity and cancer.

A video about the research can be viewed here.

ABOUT THE RESEARCH

'Pharmacological blockade of the CD39/CD73 pathway but not adenosine receptors augments disease in a humanized mouse model of graft-versus-host disease' by Nicholas Geraghty, Debbie Watson and Ronald Sluyter is published in Immunology and Cell Biology.

This project was funded by the Faculty of Science, Medicine and Health, University of Wollongong and Molecular Horizons, University of Wollongong. Debbie Watson was supported by the AMP Tomorrow Fund.