Receptor selective retinoids promote monocyte (Mo) differentiation to mature dentritic cells (DC) in peripheral blood of cancer patients.
R. Porta, M. M. Dikov, J. M. Amann, D. P. Carbone;
Vanderbilt Ingram Cancer Center, Nashville, TN
Abstract: Background: Abnormal differentiation of DC and impaired antigen-presenting function in cancer patients is an important mechanism of tumor escape from immune surveillance.
In the current study, we have investigated whether retinoids can induce Mo differentiation into DC and used receptor-selective ligands to characterize the retinoid receptors involved.
Methods: We isolate CD14+Mo from the peripheral blood of cancer patients or normal donors using immunomagnetic separation techniques (MACS system). Cells were then cultured for 4 to 6 days in the presence of 30ng/ml GM-CSF with or without receptor-selective retinoids ( Ligand Pharmaceuticals, Inc.) or pan-specific 9-cis-trans-retinoic acid as control.
Cell phenotype and number were assessed by flow cytometry. Results: At a concentration of 1 ìM, RARá and RARâ/ã-specific compounds effectively promoted differentiation of Mo into DC as characterized by expression of DR , CD86, CD1c and CD83 cell surface markers, with 18%-53% of cells acquiring these markers.
RXR-selective compounds were minimum effective, inducing expression in only 0.7%-13% of cells.
Conclusions: These data indicate that Mo can be differentiated into DC by retinoid treatment and specifically those selective for RAR.
Abstract No: 2527
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