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.