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 sho wed that the peripheral blood CD34(+) cells of HNSCC patients are capable o f differentiating into dendritic cells. Because CD34(+) cells can different iate through several pathways into dendritic cell subpopulations, the inter mediate cells through which the blood CD34(+) cells of HNSCC patients diffe rentiate 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 a, 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 t hat have been described for cord blood CD34(+) cells. To functionally analy ze whether these populations were in fact precursor cells, they were isolat ed 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 int o cells that resembled dendritic cells, although a higher proportion develo ped 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 increas ed iu. HNSCC patients can develop into both committed and bipotential dendr itic precursor cells, which carl subsequently give rise to dendritic cells.