RESUMEN
Impairing dendritic cell (DC) function to prevent graft versus host disease (GvHD) is an appealing concept. DC antigen presentation is NF-κB pathway-dependent and bortezomib might therefore play a role in preventing alloreactivity. We obtained DC from the blood of patients enrolled in a phase I study using post-transplant cyclophosphamide and bortezomib for prevention of GvHD. Control samples were obtained from patients receiving standard GvHD prevention regimen. Pre-treatment samples were also collected from enrolled patients. DC isolated on days +1, +4, and +7 showed progressive decrease in the expression of maturation markers in comparison to control. In a DC-CD4+ mixed lymphocyte reaction (MLR) where DC isolated from the recipient blood before graft infusion were the stimulator cells, T cell proliferation measured by bromodeoxyuridine (BrdU) integration was decreased in samples obtained on days +14 and +21 in comparison to control group. Finally, measured by real-time PCR, the expression of IκB progressively increased while the expression of NF-κB decreased in DC on days +1, +4, and +7, in comparison to pre-treatment paired controls. We conclude that our data further justify exploring the role of bortezomib in GvHD prevention and propose a novel mechanism of action of bortezomib in DC.
