Treg trafficking may help preserve GVL while limiting GVHD after HSCT

Researchers studied Treg/Tcon immunotherapy in a xenogeneic model in which mice engrafted with human acute myeloid leukemia received allogeneic human peripheral-blood regulatory T cells (Tregs), followed by conventional T cells (Tcons). They also assessed a major histocompatibility complex–mismatched mouse transplant model and T-cell–depleted haploidentical transplant patients who received the immunotherapy. The endpoints included leukemia control, GVHD, and the distribution and activity of the infused cells.

In the models, the treatment cleared leukemia without causing GVHD. Peripheral-blood Tregs, which were largely CD45RO+ and expressed low levels of the CXCR4 bone-marrow homing receptor, were found in peripheral tissues but not in bone marrow. Tcons retained leukemia-killing activity in marrow, while their alloreactivity appeared suppressed in peripheral tissues. In patients, infused Tregs were not detected in marrow during the first month after transplant, whereas donor Tcons homed there. The findings suggest a trafficking-based mechanism, but do not establish that treatment should change; the clinical observations and preclinical models limit conclusions about patient outcomes.