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July 23, 2020 // --- In a new study, researchers at the University of Miami Miller School of Medicine, the University of Minnesota and the University of Florida found that inhibiting the STING protein pathway protects some patients from graft sversus host disease, GVHD, the most serious complication of bone marrow (stem cell) transplantation.
related findings were published on July 15, 2020 in the journal Science Translational Medicine, with the title "STING differentially regulates the tc GVHD by CD8 versus CD4 T cell subsets".
the paper's author is Dr. Robert Levy of the Miller School of Medicine at the University of Miami.
the first author of the paper was Cameron Bader, a graduate student at the Miller School of Medicine at the University of Miami.
images from Science Translational Medicine, 2020, doi: 10.1126/scitranslmed.ay5006. "This pathway plays a very important role in allogeneic (donor) stem cell transplantation," said Dr.
Levy.
in a preclinical model of transplants simulated in patients matched by HLA (human leukocyte antigen), we wanted to interfere with the STING pathway to minimize GVHD and complications associated with the disease.
"Given that aggressive chemotherapy is used to destroy the patient's own bone marrow cells, allogeneic bone marrow transplants, i.e. new hematopoietic cells obtained by patients from the donor, are usually the main components of leukemia and lymphoma treatment."
However, the donor's cells can also produce their own immune response, allowing these transplanted cells to fight against their new hosts.
GVHD can cause rashes, nausea, diarrhea and liver damage, which are the main causeof non-recurrent deathinos in these patients.
in this paper, Dr Levy and his team tested whether STING can be regulated to control GVHD.
in one example, they built a model of an allogeneic transplant that mimics sibling matching, and found that GVHD's symptoms were alleviated when STING was missing.
however, when studying STING in a transplant model that is not closely related to the donor and recipient, the absence of the STING pathway can make GVHD worse. further research
showed that this surprising difference was caused by different immune system T-cells.
when only CD8 T cells were transplanted, not CD4 T cells, Levy's lab replicated positive results in an unmatched transplant model, reducing the symptoms of GVHD. "This tells us that the cell population of mediated GVHD does affect the role of STING in these grafts," said Dr. levy,
.
STING can make GVHD worse, or it can also provide protection.
we found that when CD8 T cells were present in the graft, they removed the antigen-presentation cells that activate cd4 T cells.
so if you remove these antigen-presentation cells, you won't activate the CD4 T cells, and you can also reduce GVHD.
" Dr Levy believes that inhibiting STING in matching patients may reduce their risk of developing GVHD.
, however, there may be an added benefit: STING can also activate T cells after enhancement and promote a stronger immune response to cancer cells.
in this case, clinicians may want to selectively inhibit and enhance STING at different times when treating cancer patients. "For our fellow patients, like our preclinical model, we wanted to block STING early in the transplant to prevent the presence of severe GVHD," dr.
Levy said.
later, we may want to activate STING to help produce an anti-tumor immune response to residual leukemia or lymphoma cells.
" (Bioon.com) References: 1.Cameron S. Bader et al. STING differentially regulates s ybs a GVHD mediated by CD8 versus CD4 T cell subsets. Science Translational Medicine, 2020, doi: 10.1126/scitranslmed.ay5006.2. Sylvester researchers cys cyn n it's mightease graft versus host disease.