Fig. 6
From: Beyond T-cell subsets: stemness and adaptation redefining immunity and immunotherapy
Stem-like T cells resist calcineurin inhibitor (CNI) therapies. In the context of allogeneic hematopoietic stem cell transplantation (HSCT), CNIs suppress the differentiation of stem-like T cells into both effector and terminally exhausted (TEX) cells. Instead, CNIs promote the persistence of memory-like T cells and transitory TEX cells. This diversion away from terminal differentiation is associated with reduced GVHD during treatment. However, both memory-like and transitory TEX cells retain their proliferative capacity and alloreactivity. Upon PD-1 blockade or CNI withdrawal, these cells can differentiate into pathogenic effector T cells, resulting in GVHD recurrence. Thus, while CNIs prevent terminal differentiation and exhaustion, they fail to eliminate the stem-like T-cell pool, highlighting their limitations in achieving durable immune tolerance. Created with BioRender.com
