Researchers have gifted the patients of leukemia and lymphoma with a possible yet expensive treatment, called bone marrow transplant (BMT). The function of the T and B cells of the bone marrow is specifically to protect the receiver from foreign invasions. Thus these helpful cells also aid in protecting receivers body from developing cancer cells. However, this treatment with its positive side also holds some risks.
The T cells mistakenly can recognize the recipient normal body cells as foreign particles and can attack them. This condition is known as the graft-vs-host disease (GVHD). It can lead the recipient to serious health complications thus in return reducing the overall health of the patient.
One of the possible ways to suppress the functioning of the T cells in GVHD is to administer the patient’s body with possible drugs and medications. But this can cause the recipients’ body to be more prone to infections and recurring of cancer cells. Even after going through this treatment 30 to 50% of the patients still develop acute GVHD and around 70% of the patients get chronic GVHD.
Xue-Zhong Yu, M.D., head of the Department of Microbiology and Immunology in the College of Medicine at the Medical University of South Carolina (MUSC) and SmartState Endowed Chair in Cancer Stem Cell Biology and Therapy at Hollings Cancer Center said: “GVHD can be expected to occur in the majority of transplanted patients. More treatment options are desperately needed.”
An MUSC research team was led by Yu who identified a type of enzyme which can possibly control GVHD without the chances of recurring cancer. The enzyme Sirt-1 was somehow able to inhibit the functioning of the T cells in mice without disturbing other mechanisms. The findings were published online in the Journal Blood on 4th December 2018.
As per the findings, mice who received Bone marrow treatment plus Sirt-1 inhibitor lived better as well as longer; and scored much higher in the clinical trials than the mice that went through the treatment but did not have Sirt-1 enzyme. Researchers concluded that this effect is due to the T cells.
Yu said: “What’s exciting about our study is that Sirt-1 regulates different subsets of T cells differently. So by inhibiting it, we can suppress T cells that lead to GVHD without affecting those that protect against tumor relapse. Also, blocking Sirt-1 could be effective in preventing both acute and chronic GVHD.”
There is a huge difference between acute and chronic GVHD, they are distinguished mainly on the basis of their starting time as well as on their symptoms. Acute GVHD only attacks the person only in the first months of the transplant while in chronic GVHD the patients get deprived of a good quality of life on a long term basis. These past few years have improved the condition for acute GVHD but treatment for chronic GVHD is still under consideration.
Chronic GVHD can cause organ failure due to the formation of fibrosis (scarring of the organs). In the study, Sirt-1 inhibitor showed a positive response in mice for chronic GVHD too. In this disease, B cells start overworking that is they grow more than normal rate. It was observed that Sirt-1-deficient T cells play its role in reducing the overworking of B cells as well as in their activation.
Anusara Daenthanasanmak, Ph.D., a medical student in the Yu lab during the trial and is now at the National Institutes of Health said: “This indicates that Sirt-1 plays an important role in T- and B- cell interaction in GVHD development,” “By blocking Sirt-1 activity, we could have a potential treatment for both acute and chronic GVHD.
Yu and his team members are eager to know to get a better understanding of Sirt-1 and their part in controlling B cells. “B cells are critical in the pathogenesis of chronic GVHD,” says Yu. “That is still a gap we need to fill in.” As per the analysis, findings are strong enough to support patients care but researchers still consider that more work should be done before implying the method on humans.
“I hope to be able to translate the findings in my lab to the clinic,” says Yu. “But, first, further studies are needed to examine the role of Sirt-1 in human T cells and in a human setting, assessing correlations in patients.”