In the Right Place and the Right State: Spatial Cross-Talk and Immune State Dictate Leukemia Response to Immunotherapy.

Abstract

Donor lymphocyte infusion (DLI) is a crucial therapeutic strategy for relapsed myeloid malignancies after allogeneic hematopoietic cell transplantation, leveraging the graft-versus-leukemia (GvL) effect to restore immune control. Although highly effective in chronic myeloid leukemia, its efficacy in acute myeloid leukemia remains limited, with underlying mechanisms not fully understood. Recent research by Maurer and colleagues utilized cutting-edge technologies to dissect immune-leukemia interactions within the bone marrow niche, identifying a cytotoxic CD8+ T-cell population as a key mediator of the antileukemic response. The study highlights a dynamic expansion of T and NK cells in responders, whereas nonresponders display an immune suppressive bone marrow niche. T-cell receptor tracking revealed that the primary effectors of GvL in acute myeloid leukemia originate from the DLI, yet their activation depends on a permissive bone marrow microenvironment. These insights emphasize that leukemia progression and immune response are shaped not only by malignant cells but also by broader niche dynamics. Further investigation is needed to define the different mechanisms that drive response or resistance to cellular therapies but also to dissect the antigenic specificity of GvL-mediating T cells and define biomarkers predicting response to DLI.