Reduced Plasmacytoid Dendritic Cell Output Is Associated With High Risk in Low-grade Myelodysplastic Syndrome

Plasmacytoid Dendritic Cells, a Novel Target in Myeloid Neoplasms

“…MPDCP is rare, but not systematically screened in routine hospital practice. It was reported in association with CMML, AML or MDS; more recently it has been referred to as pDC-CMML [ 99 ], pDC-AML [ 3 , 4 ] and pDC-MDS [ 100 ], respectively. The ontogeny of pDCs is unclear [ 9 ], but a clonal maturation from blasts to pDCs in AML was suggested [ 101 , 102 ].…”

“…The ontogeny of pDCs is unclear [ 9 ], but a clonal maturation from blasts to pDCs in AML was suggested [ 101 , 102 ]. However, tumor infiltration by pDCs from the bone marrow microenvironment in hematological disease could be also suggested [ 100 ], as reported in solid cancers. Functions of pDCs in those entities may differ between a blastic maturation into pDCs and a mature pDC infiltration in the tumor microenvironment.…”

“…Concerning immune checkpoint expression, cDC1 in MDS from BM showed a high upregulation of ILT2 and a downregulation of TIM-3 [ 128 ]. Recently, two studies have provided updated knowledge about pDCs in MDS [ 100 , 129 ]. In the first one, DC subset proportions were lower in MDS BM than in healthy donor BM [ 129 ].…”

“…Proliferation of CD4 + and CD8 + T-cells was reduced for all MDS subsets, which might suggest a negative interaction with pDC by tolerogenic functions. In opposition, in the second study, low pDC rate was associated with an inferior outcome for low- and high-grade MDS [ 100 ], suggesting an immunogenic function of pDCs. This reflects the complex balance between the tolerogenic and immunogenic functions of pDCs, with antagonistic roles according to the importance of the pDC infiltrate.…”

“…This reflects the complex balance between the tolerogenic and immunogenic functions of pDCs, with antagonistic roles according to the importance of the pDC infiltrate. Sorted pDC showed a mixture of neoplastic and normal cells by fluorescence in situ hybridization, suggesting clonal evolution but also a differentiation blockade from myeloid blast to pDCs [ 100 ]. In addition, ex vivo culture of pDCs induced a limited rate of pDCs.…”