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E Lubbers

Publications and source records attributed to E Lubbers.

3 recordsLinked to original sources

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.

Antigens, CD1↗

Cultures derived from peripheral blood CD34+ progenitor cells of head and neck cancer patients and from cord blood are functionally different.

Patients with head and neck squamous cell carcinoma (HNSCC) have profound immune defects mediated, in part, by an increased number of immune suppressive CD34+ progenitor cells in their peripheral blood and tumor. One means of overcoming this immune suppression is to stimulate the CD34+ cells to differentiate into more mature, nonsuppressive progeny such as dendritic cells or monocytes. This study determined that CD34+ cells from the peripheral blood of HNSCC patients have the same potential to differentiate into dendritic cells as do human umbilical cord blood CD34+ cells following 12-16 days of culture with a cytokine cocktail. When compared functionally, the cultures that developed from CD34+ cells of cord blood were able to induce an allostimulatory response in naive T-cells, while the cultures that developed from patient CD34+ cells lacked allostimulatory ability. Both cultures expressed class II MHC (HLA-DR), but the proportion of cells expressing the costimulatory molecules CD80 and CD86 was significantly less in cultures that developed from HNSCC-patient CD34+ cells. Therefore, although the CD34+ cells from the peripheral blood of HNSCC patients can differentiate into dendritic cells, their allostimulatory capabilities are impaired, raising the question of their potential effectiveness in stimulating antitumor immune responses.

Antigens, CD34↗