From Immune Dysregulations to Therapeutic Perspectives in Myelodysplastic Syndromes: A Review

Abstract

The pathophysiology of myelodysplastic syndromes (MDSs) is complex and often includes immune dysregulation of both the innate and adaptive immune systems. Whereas clonal selection mainly involves smoldering inflammation, a cellular immunity dysfunction leads to increased apoptosis and blast proliferation. Addressing immune dysregulations in MDS is a recent concept that has allowed the identification of new therapeutic targets. Several approaches targeting the different actors of the immune system have therefore been developed. However, the results are very heterogeneous, indicating the need to improve our understanding of the disease and interactions between chronic inflammation, adaptive dysfunction, and somatic mutations. This review highlights current knowledge of the role of immune dysregulation in MDS pathophysiology and the field of new drugs.

Keywords: T-cell; immune; inflammation; myelodysplastic syndromes.

Figure 1

From immune dysregulations to therapeutic perspectives in myelodysplastic syndromes. (A) Immune key hubs involved in early stages, low-risk MDS, and high-risk MDS. (B) Available and potential drugs targeting immune system in MDS. CD: Cluster of Differentiation; CTLA-4: Cytotoxic T-Lymphocyte Antigen 4; DAMPs: Damage Associated Molecular Patterns; Del5q: Deletion 5q; DNMT3A: DNA methyl-transferase 3A; Gal9: Galectin 9; HR-MDS: High-risk myelodysplastic syndrome; IL: Interleukin; LR-MDS: Low-risk myelodysplastic syndrome; M1/M2: Macrophages type 1 and 2; MDSC: Myeloid-Derived Suppressor Cells; NKG2D: Natural killer group 2 member; NLRP3: NOD-like receptor family, pyrin domain containing 3; PD-1: Program cell death-1; PD-L1: Program cell death-Ligand 1; RANTES: Regulated upon Activation, Normal T Cell Expressed and Presumably Secreted; SF3B1: Splicing Factor 3b Subunit 1; SRSF2: Serine and Arginine Rich Splicing Factor 2; TET2: Ten-eleven-translocation 2; TIGIT: T cell immunoreceptor with Ig and ITIM domains; TIM3: T-cell immunoglobulin and mucin containing protein-3; TGF-β: Transforming Growth Factor-β; TLR: Toll Like Receptor; TNF-α: Tumor Necrosis Factor-α; TNFR: Tumor Necrosis Factor Receptor; TP53: Tumor Protein 53; Treg: Lymphocytes T regulators; WT1: Wilms Tumor 1.