Contemporary understanding of myeloid-derived suppressor cells in the acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) tumor microenvironment.

Abstract

Introduction: Myeloid-derived suppressor cells (MDSCs) are a key immunosuppressive component in the tumor microenvironment, contributing to immune evasion and disease progression in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).

Areas covered: We searched PubMed for literature that evaluated the effect of MDSCs in myeloid diseases. MDSCs impact outcomes by facilitating leukemic stem cell survival, impairing immune checkpoint efficacy, and modulating the bone marrow niche. While these immunosuppressive properties can mitigate graft-versus-host disease post-transplantation, sustained MDSC-mediated immunosuppression can also increase the risk of leukemia relapse.We review MDSC development and function, including metabolic reprogramming, epigenetic modifications, and cytokine-mediated pathways. Therapeutic strategies targeting MDSCs, such as depletion, functional reprogramming, and inhibition of key metabolic and immune pathways, show promising data in preclinical models. However, clinical translation remains hindered by challenges in MDSC quantification and standardization of functional assays. This review underscores the potential of combining MDSC-targeted therapies with conventional and novel treatments to improve patient outcomes in AML and MDS.

Expert opinion: Future studies should focus on standardizing MDSC assessment, elucidate their dynamic roles in therapy, and optimize combination approaches for clinical application.