[Donor T cell exhaustion and immune tolerance after allogeneic hematopoietic cell transplantation].

Allogeneic hematopoietic cell transplantation (allo-HCT) is a curative treatment for hematologic malignancies. However, graft-versus-host disease (GVHD) and disease relapse negatively impact prognosis. Chronic GVHD significantly affects both prognosis and quality of life, making its prevention crucial. The current standard GVHD prophylaxis, using calcineurin inhibitors (CNIs) and methotrexate (MTX), is effective against acute GVHD but its effect on chronic GVHD is limited. The mechanism by which CNIs fail to prevent chronic GVHD has long been unclear. Recently, we conducted single-cell RNA sequencing of donor T cells after mouse HCT and found that CNIs inhibit donor T-cell exhaustion while inducing effector-like exhausted T cells. These cells contribute to the development of chronic GVHD after allo-HCT and play a role in enhancing graft-versus-leukemia (GVL) effects after post-HCT PD-1 blockade. We are currently accumulating and analyzing patient samples to validate our findings from the mouse HCT models.