The following is a summary of “Highly immunosuppressive myeloid cells correlate with early relapse after allogeneic stem cell transplantation,” published in the May 2024 issue of Hematology by Notarantonio et al.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) stands as the sole curative option for myeloid malignancies like acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS), leveraging the graft-versus-leukemia effect (GVL) to eradicate malignant clones. However, despite its efficacy, relapse remains a daunting challenge, primarily attributed to HLA loss or downregulation and the upregulation of inhibitory ligands on leukemic blasts, culminating in donor immune effector dysfunctions.
From 2018 to 2021, researchers undertook a monocentric prospective study encompassing 61 consecutive patients who underwent transplantation for AML or high-risk MDS. Longitudinal assessments of bone marrow and peripheral blood immune cells were conducted at days +30, +90, and +180 post-transplantation. Specifically, the study group scrutinized the interplay between myeloid-derived suppressor cells (MDSCs) and T-cells.
Among the 61 patients, 45 remained free from relapse during the initial 12 months, whereas 16 experienced relapse within the same timeframe. Comparative analyses with healthy donors revealed a heterogeneous rise in MDSC frequency from months 1 to 6 post-transplantation across all recipients, with the granulocytic subset emerging as predominant. Notably, relapsed patients exhibited highly immunosuppressive MDSCs in peripheral blood as early as day +30, characterized by an activated NLRP3 inflammasome signature. Importantly, a statistical correlation was observed between circulating immunosuppressive MDSCs and the presence of circulating double-positive Tim3+LAG3+ exhausted T cells.
The findings underscore the potential utility of a simple in vitro functional assay to delineate MDSC immunosuppressive properties, serving as an early biomarker for relapse. This raises intriguing prospects for future novel preventive strategies targeting MDSCs, potentially augmenting the efficacy of allo-HSCT in mitigating relapse risk in myeloid malignancies.
Source: ehoonline.biomedcentral.com/articles/10.1186/s40164-024-00516-4