Myelodysplastic syndrome (MDS), which can progress into acute myeloid leukemia, is a cancer in which the bone marrow doesn’t produce blood cells properly. MDS is associated with deficiency of immune cells called lymphocytes, particularly T cells and natural killer (NK) cells, but its specific mechanism is unclear. To learn more, researchers recently examined the lymphocyte populations in patients with MDS. Compared to healthy controls, patients with MDS had fewer NK cells, especially patients with more severe disease. Patients with MDS also had reduced NK cell function, as indicated by downregulation of NK cell–activating receptors and upregulation of the NK cell–inhibiting receptor TIGIT. Bone marrow mesenchymal stem cells (BMSCs) from patients with MDS expressed high levels of the TIGIT-binding molecule CD155 and in vitro experiments revealed that BMSCs can interact with NK cells, suggesting a pathogenic role of BMSCs in MDS. However, blocking TIGIT helped to restore the function of NK cells from patients with MDS. Although in vivo studies are needed, the findings reveal that BMSCs mediate NK cell dysfunction in MDS via CD155/TIGIT signaling providing new insights and potential targets for MDS treatment.