The Mechanism of Activated TGF-β1 Inhibiting GVL Effects of Bone Marrow NK Cells Leading to Early Relapse after Transplantation

Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is one of the best ways to cure acute myeloid leukemia (AML). However, patients with AML undergoing allo-HSCT are at risk of relapse, the mechanism remains poorly understood. Here, we demonstrated the significant decrease of nature killer (NK) cells, and the declined proportion of multi-functional effector NK cells in bone marrow from patients who had a relapse in 3 months after allo-HSCT. Furthermore, we verified the levels of activated Transforming growth factor-β1 (TGF-β1), not the total TGF-β1, increased in bone marrow of these patients. This high level activated TGF-β1 was correlated with reduced cytotoxicity of NK cell, and contributed to immune escape of tumor cells. Moreover, the expression of glycoprotein A repetitions predominant (GARP), which is critical to TGF-β1 activation, high expressed in CD4⁺ T cells of patients who had a relapse. These data reveal a mechanism of immune escape and proposes approaches for therapeutic administration of NK cells in order to reverse suppression of activated TGF-β1 during early allo-HSCT.