Therapeutic benefits targeting B-cells in chronic graft-versus-host disease

Allogeneic hematopoietic cell transplantation (allo-HCT) can be a curative strategy for hematological diseases, and the indications for allo-HCT have broadened widely due to recent progress in supportive strategies. However, patients must overcome various complications and chronic graft-versus-host disease (cGVHD) remains the most common allo-HCT cause of long-term morbidity and mortality. cGVHD is difficult to biologically assess due to the heterogeneity of cGVHD symptoms, and the pathogenesis of cGVHD has yet to be established. Recent experimental model progress has suggested that B-cells play a critical role in cGVHD development. Consistent with these experimental results, some clinical studies investigating B-cell depletion and modulation of B-cell signaling pathways have decreased cGVHD incidence and provided some therapeutic benefit. However, randomized control studies are necessary to confirm the efficacy of B-cell targeting drugs for cGVHD. Here, we review the pathophysiology of cGVHD, especially focusing on the role of B-cell immunity, and discuss the efficacy of both B-cell depletion and modulation of B-cell signaling pathways in human cGVHD prevention, initial treatment, and salvage treatment.