Biology Reference
In-Depth Information
ch 20
The endothelium in graft-versus-
host disease and graft-versus-
leukemia
Olaf Penack
Charité University Hospital, Department of Hematology, Oncology, and Tumor Immunology, Charité
Universitätsmedizin Berlin, Berlin, Germany
479
Key points
Theendotheliumisessentialformultipleprocessesafterallo-HSCT,including
leukocytemigration,antigenpresentation,T-cellactivation,andneovascular-
ization.
NeovascularizationoccursduringtheacutephaseofGVHDanditsinhibition
canattenuateGVHDseverity.
The inhibitionofneovascularizationenhances theefficacyofadoptiveT-cell
therapiesagainstmalignanttumors.
BecauseoftheirpotentialbeneficialeffectsonGVHDandGVL,therapeutic
approachestargetingtheendotheliumafterallo-HSCTarepromising.
The endothelium in graft-versus-host disease
The endothelium forms the inner lining of blood vessels and mediates
physiological processes, such as barrier function, inflammation, and hemo-
stasis. In patients undergoing allogeneic hematopoietic stem cell transplan-
tation (allo-HSCT) the interplay between host endothelial cells (ECs) and
donor leukocytes is important for the pathophysiology of graft-versus-host
disease (GVHD). EC dysfunction is a critical process in transplant-related
complications, such as sinusoidal obstruction syndrome, capillary leak
syndrome, engraftment syndrome, transplant-associated microangiopa-
thy, diffuse alveolar hemorrhage, and idiopathic pneumonia syndrome, as
described in detail in a review article [1] .
During allo-HSCT the endothelium may be affected by multiple factors
including radiation, chemotherapy, infections, cytokines, and alloreac-
tive leukocytes. Figure 20.1 shows a three-phase model of endothelial
dysfunction during allo-HSCT, which has been proposed: [2] (a) initial
Search WWH ::




Custom Search