However, EBV reactivation was associated with a sustained alteration in NKG2A and NKG2C subsets of CD56 NK cells which might have a pathogenic role in chronic GVHD.
Analysis focused on previously identified cGVHD cellular biomarkers, including naive helper T (Th) cells, recent thymic emigrant (RTE) Th cells, CD21<sup>low</sup> B cells, CD56<sup>bright</sup> NK<sub>reg</sub> cells, and T<sub>reg</sub> cells ST2, osteopontin, sBAFF, sCD25, TIM-3, matrix metallopeptidase 3, ICAM-1, CXCL10, and soluble aminopeptidase N. The ATG-treated group had a >10-fold decrease in both RTE naive Th and naive Th cells (P < .0001) and a 10-fold increase in CD56<sup>bright</sup> NK<sub>reg</sub> cells (P < .0001).
Analysis focused on previously identified cGVHD cellular biomarkers, including naive helper T (Th) cells, recent thymic emigrant (RTE) Th cells, CD21<sup>low</sup> B cells, CD56<sup>bright</sup> NK<sub>reg</sub> cells, and T<sub>reg</sub> cells ST2, osteopontin, sBAFF, sCD25, TIM-3, matrix metallopeptidase 3, ICAM-1, CXCL10, and soluble aminopeptidase N. The ATG-treated group had a >10-fold decrease in both RTE naive Th and naive Th cells (P < .0001) and a 10-fold increase in CD56<sup>bright</sup> NK<sub>reg</sub> cells (P < .0001).
Analysis focused on previously identified cGVHD cellular biomarkers, including naive helper T (Th) cells, recent thymic emigrant (RTE) Th cells, CD21<sup>low</sup> B cells, CD56<sup>bright</sup> NK<sub>reg</sub> cells, and T<sub>reg</sub> cells ST2, osteopontin, sBAFF, sCD25, TIM-3, matrix metallopeptidase 3, ICAM-1, CXCL10, and soluble aminopeptidase N. The ATG-treated group had a >10-fold decrease in both RTE naive Th and naive Th cells (P < .0001) and a 10-fold increase in CD56<sup>bright</sup> NK<sub>reg</sub> cells (P < .0001).
Analysis focused on previously identified cGVHD cellular biomarkers, including naive helper T (Th) cells, recent thymic emigrant (RTE) Th cells, CD21<sup>low</sup> B cells, CD56<sup>bright</sup> NK<sub>reg</sub> cells, and T<sub>reg</sub> cells ST2, osteopontin, sBAFF, sCD25, TIM-3, matrix metallopeptidase 3, ICAM-1, CXCL10, and soluble aminopeptidase N. The ATG-treated group had a >10-fold decrease in both RTE naive Th and naive Th cells (P < .0001) and a 10-fold increase in CD56<sup>bright</sup> NK<sub>reg</sub> cells (P < .0001).
Moreover, our data show that aGVHD, cGVHD patients and healthy donors (HDs) present distinct NK patterns: aGVHD patients have a higher frequency of CD56<sup>bri</sup> NK subsets with stronger NKG2D and CD62L expression, while CD56<sup>-</sup>CD16<sup>+</sup> NK cells with higher expression of CD57 and CD11b stand out as a signature population for cGVHD.
In the MSD group we found a trend for less extensive cGVHD in patients receiving FB2 with in vivo TCD, HR: 0.49, p = 0.08, and in those without worse NRM, HR: 2.14, p = 0.04, and a trend for more total cGVHD, HR: 1.61, p = 0.09.
We hypothesized that galectin-3, Mac-2 binding protein (M2BP), or Wisteria floribunda agglutinin (WFA)+-M2BP, called M2BP glycan isomer (M2BPGi), might contribute to macrophage activation, and fibrosis would be associated with cGVHD and nonrelapse mortality (NRM) in hematopoietic stem cell transplant (HSCT) recipients.
WT APC can potentially cleave protease-activated receptor 1 (PAR1) at Arg41 or Arg46, the latter causing anti-inflammatory signaling. cGVHD was reduced in recipients of T cells from WT PAR1 or mutated Gln41-PAR1 donors but not from mutated Gln46-PAR1 donors.
We created humanised mice model for chronic GVHD (cGVHD) by injecting cord blood (CB)-derived human CD34<sup>+</sup>CD38<sup>-</sup>CD45RA<sup>-</sup> haematopoietic stem/progenitor cells (HSPCs) into hIL-6 transgenic NOD/SCID/Il2rgKO (NSG) newborns, and compared GVHD progression with NSG newborns receiving CB CD34<sup>-</sup> cells mimicking acute GVHD.
Collectively, these data show that control of anti-SLAMF3-induced signaling is requisite to prevent autoantibody responses during cGVHD, but reduces responses to foreign antigens.
Notably, the expanded Tregs were instrumental to GM-CSF-mediated cGVHD inhibition, which was dependent upon an increased ratio of Tregs to conventional T cells rather than augmentation of suppressive function.
Itacitinib is a potent, selective JAK-1 inhibitor currently in phase 3 development for the treatment of acute and chronic graft-versus-host disease (GVHD) in combination with corticosteroids.
In conclusion, Sirt-1 is a promising therapeutic target for the control of aGVHD and cGVHD pathogenesis and possesses high potential for clinical application.