The best course of treatment for certain patients with acute myeloid leukemia (AML) is allogeneic hematopoietic stem cell transplantation (allo-HSCT), which depends on a “graft-versus-leukemia” effect (GVL) where donor T cells mediate inhibition of malignant cell proliferation.

Relapse, however, continued to be the leading cause of mortality following allo-HSCT. Numerous immunoregulatory mechanisms, such as ligand-mediated engagement of inhibitory receptors (IRs) on effector cells and induction of immunosuppressive cell subsets like regulatory T cells (Tregs) or myeloid-derived suppressor cells (MDSCs), have been demonstrated to inhibit antitumor immunity in a variety of malignancies. Relapse following HSCT still presents a significant treatment challenge, although further research is required to better understand the immunoregulatory systems that limit the GVL impact. After allo-HSCT, researchers thoroughly characterized the circulating leukocytes in 2 patient cohorts by mass cytometry. They first longitudinally examined many immunoregulatory characteristics to identify particular patterns, revealing differences between MDSCs and Tregs, for example.

In general, the immunological environment was constant during 3-6 months. However, there were significant changes from 6 to 12 following HSCT. Significant immunological equilibrium changes were maintained a year following HSCT, as evidenced by comparison to healthy persons. Importantly, in a second cross-sectional cohort, they discovered that high TIGIT & CD161 expression levels on CD4 T cells at month 3 following HSCT were separate traits substantially linked with a subsequent AML recurrence.

Together, the results offered a comprehensive understanding of the immunoregulatory landscape’s reconstitution following HSCT and indicated non-canonical IRs linked to relapse, which may pave the way for novel prognostic indicators or therapeutic targets to boost anti-AML immunity that has been compromised.