Landscape of alterations in the checkpoint system in myelodysplastic syndrome and implications for prognosis.
Ivan Sergeevich MoiseevNikolai TcvetkovOlga EpifanovskayaElena BabenkoAnna ParfenenkovaEvgenii BakinKsenia YurovskayaElena MorozovaPublished in: PloS one (2022)
The emergence of novel immunotherapies for myelodysplastic syndrome (MDS) calls for a profound characterization of the "immunome" in the bone marrow (BM) and evaluation of prognostic impact of immunological changes. We performed a prospective study of 87 MDS patients who were referred to a tertiary hematological center and of 11 bone marrow donors who were not related to the study cohort. A flow cytometry panel with 48 markers including checkpoint ligands and receptors was used to study lymphoid and myeloid subpopulations in the bone marrow aspirates. The study found that both the healthy donors and the MDS patients have a high proportion of lymphocytes with PD-1 expression (41±18% and 58±25% respectively) and a high proportion of myeloid cells with PD-1L expression (31±23% and 12±7% respectively), indicating a potential physiological role of checkpoint systems in BM. At the same time, complex alterations including PD-1, CTLA-4, LAG-3 and TIM3 pathways accompanied by an increased level of T-reg and myeloid derived suppressor cell populations were identified in the BM of MDS patients. Cluster analysis showed independent prognostic significance of the checkpoint profile for overall survival (HR 1.90, 95%CI 1.01-3.56, p = 0.0471). TIM3-postive NK and CD8 effector cells along with the blast count were the key subpopulations for prognosis. An elevation of blasts in the bone marrow was associated with simultaneous expression of multiple checkpoints on myeloid cells.
Keyphrases
- bone marrow
- induced apoptosis
- dna damage
- mesenchymal stem cells
- end stage renal disease
- cell cycle
- ejection fraction
- cell cycle arrest
- newly diagnosed
- poor prognosis
- chronic kidney disease
- flow cytometry
- dendritic cells
- prognostic factors
- single cell
- stem cells
- cell proliferation
- endoplasmic reticulum stress
- autism spectrum disorder
- oxidative stress
- peripheral blood
- immune response
- risk assessment
- climate change
- drug induced