In the treatment of leukemia, stem cell transplantation subsequent to
chemotherapy and radiation can often engender severe adverse inflammatory
reactions—especially in the skin or in the gut, since these so-called barrier
organs are more frequently affected. Up until now, the reason for this was
unclear. A MedUni Vienna team led by Georg Stary and Johanna Strobl from
MedUni Vienna's Department of Dermatology, the CeMM Research Center for
Molecular Medicine of the Austrian Academy of Sciences and the Ludwig
Boltzmann Institute for Rare and Undiagnosed Diseases has now identified an
immune mechanism that is partially responsible for this. The results have now
been published in the leading journal Science Translational Medicine.
The term leukemia is used to describe a group of malignant diseases of the
haematopoietic system, in which precursors of the white blood cells
(leucocytes) proliferate uncontrollably. Chemotherapy and radiotherapy are
used to destroy the abnormal blood cells, which are then replaced by means
of a stem cell transplant. In leukemia, the transplantation of healthy bone
marrow stem cells or haematopoietic stem cells is often the only hope of
recovery for patients. The process involves "replacing" all the recipient's
blood cells that were previously destroyed by the treatment with donor
cells.
However, the MedUni Vienna dermatologists have now found that there are
so-called skin-resident and inactive T cells in the endogenous immune system
that survive chemotherapy and radiotherapy intact and go on to survive for a
further ten years between and beneath the epithelial cells of the skin,
while the circulating T cells are destroyed.
"We were able to demonstrate that T cells surviving in the skin tissue are
responsible for the inflammatory reaction following a stem cell transplant.
These phenomena often occur within the first 100 days and can cause anything
from mild eczema through to extensive fibrosis, hardening of the tissue, or
blistering on the surface of the skin. In other words, the endogenous T
cells attack the recipient (host) following stem cell transplantation." In
specialist jargon, the condition is also referred to as Graft versus Host
Disease (GvHD), and, for the first time, this study identified an inverse
"Host-versus-graft reaction."
There were also cases in which the donor T cells further "supported," and
thus intensified, this reaction. Affected patients are treated with
cortisone, which causes an additional burden for patients who are already
immunosuppressed following the transplantation. The study found that in
patients who do not develop graft-versus-host disease, tissue-resident T
cells remaining after treatment even proved to be beneficial to the
recipient, in that they assumed their role in immune defense and protecting
against infection.
In the future, the exemplary study results could lead to new treatment
strategies that help to avoid, or at least to minimize, undesirable and
violent inflammatory reactions following stem cell transplants by
manipulating the recipient's inactive T cells in advance. In addition, the
manipulation of tissue-resident T cells might lead to new therapeutic
approaches for other chronic inflammatory skin diseases, such as psoriasis
or neurodermatitis.
Reference:
Johanna Strobl et al. Long-term skin-resident memory T cells proliferate in
situ and are involved in human graft-versus-host disease, Science
Translational Medicine (2020). DOI:
10.1126/scitranslmed.abb7028
Tags:
Medical Science