Dendritic cell differentiation pathways of CD34+ cells from the peripheral blood of head and neck cancer patients.
Patients with head and neck squamous cell carcinoma (HNSCC) have increased levels of immune-suppressive peripheral blood CD34+ cells. This study showed that the peripheral blood CD34+ cells of HNSCC patients are capable of differentiating into dendritic cells. Because CD34+ cells can differentiate through several pathways into dendritic cell subpopulations, the intermediate cells through which the blood CD34+ cells of HNSCC patients differentiate were identified. After 6-7 days of culturing the CD34+ cells of HNSCC patients with granulocyte-macrophage colony-stimulating factor, stem cell factor, and tumor necrosis factor at, there appeared CD14+CD1a+ and a lesser proportion of CD14(-)CD1a+ cells resembling the precursor cells of the bipotential and committed dendritic cell differentiation pathways that have been described for cord blood CD34+ cells. To functionally analyze whether these populations were in fact precursor cells, they were isolated and cultured for an additional 10-12 days. Each of these populations was shown to function as precursor cells because they were able to develop into cells that resembled dendritic cells, although a higher proportion developed from the CD14-CD1a+ cells. In contrast, expression of the dendritic activation/maturation marker CD83 was highest on the cells that developed from CD14+CD1a+ cells. Thus, the CD34+ cells whose levels are increased in HNSCC patients can develop into both committed and bipotential dendritic precursor cells, which can subsequently give rise to dendritic cells.
Lathers
D M
DM
Department of Pathology, Loyola University Stritch School of Medicine, Maywood, Illinois, USA.
Lubbers
E
E
Wright
M A
MA
Young
M R
MR
D018949:Antigens, CD1 / Q000097:blood; D018952:Antigens, CD34 / Q000097:blood*; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000276:immunology / Q000473:pathology*; D002454:Cell Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006258:Head and Neck Neoplasms / Q000097:blood / Q000276:immunology / Q000473:pathology*; D006801:Humans; D016130:Immunophenotyping; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000473:pathology*; D018950:Lipopolysaccharide Receptors / Q000097:blood; D019089:Stem Cell Factor / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D018949:Antigens, CD1; D018952:Antigens, CD34; D018950:Lipopolysaccharide Receptors; D019089:Stem Cell Factor; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor