期刊
JOURNAL OF LEUKOCYTE BIOLOGY
卷 102, 期 2, 页码 437-447出版社
WILEY
DOI: 10.1189/jlb.5MA1116-457R
关键词
CyTOF; MDSCs; macrophages; monocyte
资金
- Nuovo-Soldati Foundation (Switzerland)
- Vanderbilt-Ingram Cancer Center (VICC) [P30 CA68485]
- VICC Ambassadors
- VICC Hematology Helping Hands award
- Tinsley R. Harrison Society
- [F31 CA199993]
- [K12 CA090625]
- [R25 CA136440-04]
- [R00 CA143231-03]
The monocyte phagocyte system (MPS) includes numerous monocyte, macrophage, and dendritic cell (DC) populations that are heterogeneous, both phenotypically and functionally. In this study, we sought to characterize those diverse MPS phenotypes with mass cytometry (CyTOF). To identify a deep phenotype of monocytes, macrophages, and DCs, a panel was designed to measure 38 identity, activation, and polarization markers, including CD14, CD16, HLA-DR, CD163, CD206, CD33, CD36, CD32, CD64, CD13, CD11b, CD11c, CD86, and CD274. MPS diversity was characterized for 1) circulating monocytes from healthy donors, 2) monocyte-derived macrophages further polarized in vitro (i.e., M-CSF, GM-CSF, IL-4, IL-10, IFN-gamma, or LPS long-term stimulations), 3) monocyte-derived DCs, and 4) myeloid-derived suppressor cells (MDSCs), generated in vitro from bone marrow and/or peripheral blood. Known monocyte subsets were detected in peripheral blood to validate the panel and analysis pipeline. Then, using various culture conditions and stimuli before CyTOF analysis, we constructed a multidimensional framework for the MPS compartment, which was registered against historical M1 or M2 macrophages, monocyte subsets, and DCs. Notably, MDSCs generated in vitro from bone marrow expressed more S100A9 than when generated from peripheral blood. Finally, to test the approach in vivo, peripheral blood from patients with melanoma (n = 5) was characterized and observed to be enriched for MDSCs with a phenotype of CD14(+)HLA-DR(low)S100A9(high) (3% of PBMCs in healthy donors, 15.5% in patients with melanoma, P < 0.02). In summary, mass cytometry comprehensively characterized phenotypes of human monocyte, MDSC, macrophage, and DC subpopulations in both in vitro models and patients.
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