Mechanisms of immune dysregulation in MDS. The MDS bone marrow microenvironment exhibits perturbations in adaptive immune effector cells, including increased CD8+ cytotoxic T-cells and Th17 cells, which promote autoimmunity, as well as decreased Treg and Th2 cells, which dampen autoimmunity, favoring upregulation of IFNγ and TNFα, which induce apoptosis mediated by TRAIL, fas, and caspase-8. Innate immune derangements in the MDS marrow include decreased type 1 innate lymphoid cells (ILC1) and NK cells and increased myeloid derived suppressor cells, which secrete IL-10 and granzyme B, and promote signaling through CD33, toll-like receptors, and CXCR2 to enhance danger-associated molecular pattern stimulation of caspase-1, which promotes cell death via pyroptosis. Image created with BioRender.com.