Circulating blood dendritic cells from myeloid leukemia patients display quantitative and cytogenetic abnormalities as well as functional impairment.
Dendritic cells (DCs) are responsible for the initiation of immune responses. Two distinct subsets of blood DCs have been characterized thus far. Myeloid DCs (MDCs) and plasmacytoid monocytes (PDCs) were shown to be able to promote polarization of naive T cells. This study shows a dramatic quantitative imbalance in both circulating blood DC subsets in 37 patients with acute myeloid leukemias. Eleven patients (30%) displayed a normal quantitative profile (MDC mean, 0.37% +/- 0.21%; range, 0.01% to 0.78%; PDC mean, 0.21% +/- 0.24%; range, 0.04% to 0.62%), whereas 22 (59%) showed a tremendous expansion of MDCs (9 patients: mean, 16.76% +/- 14.03%; range, 1.36% to 41%), PDCs (4 patients: mean, 7.28% +/- 6.84%; range, 1% to 14%), or both subsets (9 patients: MDC mean, 10.86% +/- 12.36%; range, 1.02% to 37.1%; PDC mean, 4.25% +/- 3.78%; range, 1.14% to 13.04%). Finally, in 4 patients (11%), no DC subsets were detectable. Both MDC and PDC subsets exhibited the original leukemic chromosomal abnormality. Ex vivo, leukemic PDCs, but not leukemic MDCs, had impaired capacity for maturation and decreased allostimulatory activity. Also, leukemic PDCs were altered in their ability to secrete interferon-alpha. These data provide evidence that DC subsets in vivo may be affected by leukemogenesis and may contribute to leukemia escape from immune control.
Mohty
M
M
Laboratoire d'Immunologie des Tumeurs, Université de la Méditerranée, Marseille, France.
Jarrossay
D
D
Lafage-Pochitaloff
M
M
Zandotti
C
C
Brière
F
F
de Lamballeri
X N
XN
Isnardon
D
D
Sainty
D
D
Olive
D
D
Gaugler
B
B
D000818:Animals; D023201:CD40 Ligand / Q000494:pharmacology; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D003713:Dendritic Cells / Q000276:immunology* / Q000648:ultrastructure; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D016130:Immunophenotyping; D016898:Interferon-alpha / Q000096:biosynthesis / Q000378:metabolism; D007377:Interleukin-3 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D015470:Leukemia, Myeloid, Acute / Q000097:blood* / Q000235:genetics* / Q000276:immunology; D051379:Mice; D018613:Microscopy, Confocal; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D006684:HLA-DR Antigens; D016898:Interferon-alpha; D007377:Interleukin-3; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor