CAR T
Published on July 23, 2025
Augmented CD47 expression impairs alloreactive T-cell clearance after allo-HCT
by Alex Kadhim
Researchers at the University Hospital of Erlangen, Germany, have found that alloreactive donor T-cells upregulate the immune checkpoint molecule CD47 following allogeneic hematopoietic cell transplantation (allo-HCT), which enables them to evade clearance by macrophages and contributes to the development of graft-versus-host disease (GVHD). This immune evasion mechanism prevents the phagocytosis of harmful T-cells, sustaining inflammation in affected tissues, particularly the gastrointestinal tract. The findings point to CD47 as a promising therapeutic target, and suggest that blocking CD47 with antibodies could help resolve inflammation by promoting the clearance of pathogenic T-cells.
The rationale for the study stemmed from the persistent inflammation observed in GVHD and the unclear role of phagocytosis in its resolution. Researchers hypothesized that CD47, known as a "don't eat me" signal, might protect activated donor T-cells from being phagocytosed. To test this, they analyzed transcriptomic datasets and tissue samples from patients and mouse models post-transplant, focusing on the gastrointestinal tract, a primary site of GVHD. They found marked CD47 upregulation on T-cells in the ileum of GVHD patients and in mice after allo-HCT. In vitro experiments demonstrated that CD47 expression on activated T-cells suppresses antibody-dependent cellular phagocytosis (ADCP), while blocking CD47 significantly increased T-cell clearance by macrophages.
In mouse models, administration of anti-CD47 antibodies led to a significant enhancement in T-cell phagocytosis within the gut, reduced local inflammation and increased the presence of immunosuppressive macrophage populations. This intervention also resulted in a notable improvement in survival (p < 0.01) and clinical GVHD scores. Moreover, mice receiving CD47-deficient donor T-cells exhibited significantly better outcomes, including reduced GVHD severity and prolonged survival (p < 0.005). These results identify CD47 as a critical regulator of T-cell persistence in GVHD and suggest that anti-CD47 therapy could be an effective strategy to mitigate transplant-related inflammation by restoring macrophage-mediated immune homeostasis.
Reference:
Flamann CS, Shaikh H, Matos C, et al. Augmented CD47 expression impairs alloreactive T-cell clearance after allo-HCT. Blood. Published online May 7, 2025.
http://doi.org/10.1182/blood.2023023056
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