The antigen-specific reaction of T-cells working with dendritic cells, which regulate the immune system.
Credit: National Institute of Allergy and Infectious Diseases
SYDNEY: The manipulation of specific immune cells in bone marrow transplants has left a number of patients cancer-free, giving new hope to leukemia and lymphoma sufferers, according to a recent study.
A team lead by Sébastien Maury from the Service d'Hématologie Clinique, France, has shown for the first time that by depleting the regulatory T-cell (or Treg) population in donor tissue, patients suffering from very resistant forms of cancer can achieve complete remission.
By identifying the Tregs’ influence on how a new immune system reacts to foreign elements, it’s hoped that this study will result in more successful cancer treatments using transplantation.
The challenge for new immune systems
Tregs are types of white cells called T lymphocytes, which control the activity of the immune system. When they are less active in a patient, the immune system becomes more activate and can respond better to against foreign antigens.
In the case of cancer patients receiving a donor bone marrow transplant, Tregs in the transplant can kill off cancer in the patients. This is phenomenon is known as alloimmunity, and is often crucial to the success of bone marrow transplantation.
But often when an immune system is grafted to a patient, it won't recognise the cancerous cells as foreign, and instead becomes tolerant.
Anti-tumour effect improved
Maury’s research, published in Science Translational Medicine has provided the first direct evidence that Tregs facilitate this tolerance between the donor immune system and patient cancer cells in the field of transplantation.
“It has been recognised that a principal element in the induction of immune tolerance are regulatory T-cells. We therefore attempted to eliminate them from the graft and demonstrated increased alloimmunity and increased anti-tumour effect,” says Maury.
It is this anti-tumour effect which actively kills off the cancer cells in a patient, and in most successful scenario can render them cancer-free.
Study renders patients cancer-free
Participating in this study were 17 leukemia or lymphoma patients who had received bone marrow transplants in the past, but whose cancer had since returned.
Maury and his colleagues performed transplants on each of these patients once again, using the same donors, only this time eliminating the Treg population in the donor tissue first.
In 12 of the 17 patients they observed an increase the number of cancer cells killed off by the new immune systems. Four of these patients are now cancer-free.
“This study is proof of a concept which demonstrates that regulatory T-cell manipulation can have therapeutic effects in humans,” says Maury. “It opens the way to its application in various fields in medicine where the immune system needs to be ‘tolerised’ (by adding more regulatory T-cells) in autoimmune diseases or ‘un-tolerised’ (by their elimination) in cancer.”
More cancer patients to test technique
While promising results have been reported, more research into how we can curb or treat the debilitating side effects of Treg manipulation is still needed.
"When you increase the anti-tumour effect in cancer patients, you will also increase the anti-patient effect, which can lead to death in some cases," Richard Boyd from Monash University told Cosmos. "You need to find a balance."
Further clinical trials will be undertaken to explore the depth of this strategy in cancer patients.
“This study has shown some very positive outcomes for patients involved in the clinical trials,” Robert Tindle from The University of Queensland said.
“It didn’t cure all of them, but it certainly improved the outcomes for some of the patients – four of them are now in complete remission.”
“Without this treatment all of these patients would have died, no question about it, so this is a major step forward in the research of treatments for this type of cancer patient.”
