Reduced frequencies and functional impairment of dendritic cell subsets and non-classical monocytes in myelodysplastic syndromes

In myelodysplastic syndromes (MDS) the immune system is involved in pathogenesis as well as in disease progression. Dendritic cells (DC) are key players of the immune system by serving as regulators of immune responses. Their function has been scarcely studied in MDS and most of the reported studies didn't investigate naturally occurring DC subsets. Therefore, we here examined the frequency and function of DC subsets and slan+ non-classical monocytes in various MDS risk groups. Frequencies of DC as well as of slan+ monocytes were decreased in MDS bone marrow compared to normal bone marrow samples. Transcriptional profiling revealed down-regulation of transcripts related to pro-inflammatory pathways in MDS-derived cells as compared to normal bone marrow. Additionally, their capacity to induce T-cell proliferation was impaired. Multidimensional mass cytometry showed that whereas healthy donor-derived slan+ monocytes supported Th1/Th17/Treg differentiation/expansion their MDS-derived counterparts also mediated substantial Th2 expansion. Our findings point to a role for an impaired ability of DC subsets to adequately respond to cellular stress and DNA damage in the immune escape and progression of MDS. As such, it paves the way toward potential novel immunotherapeutic interventions.

Automated summary

In myelodysplastic syndromes (MDS), the immune system plays a role in both the pathogenesis and progression of the disease. Dendritic cells (DC) are important components of the immune system and regulate immune responses. However, there is limited research on the function of DC subsets in MDS, and most studies have not investigated naturally occurring DC subsets. Our study found that the frequency of DC subsets and slan+ monocytes was decreased in MDS bone marrow compared to normal bone marrow samples. Additionally, the ability of MDS-derived cells to induce T-cell proliferation was impaired. These findings suggest that the impaired response of DC subsets to cellular stress and DNA damage may contribute to the immune escape and progression of MDS.