INCREASED PRESENCE OF CD34(-BLOOD OF HEAD AND NECK-CANCER PATIENTS AND THEIR DIFFERENTIATION INTO DENDRITIC CELLS() CELLS IN THE PERIPHERAL)

Patients with head and neck squamous cell carcinoma (HNSCC) have profo und immune deficiencies. In 65% of these patients, there is an increas ed intra-tumoral presence of immune-suppressive CD34(+) progenitor cel ls. The goal of the present study was to determine whether CD34(+) cel l levels were also increased in the peripheral blood of HNSCC patients and if these immune-suppressive cells could be differentiated into de ndritic cells. Our results showed that CD34(+) cell levels are increas ed in the peripheral blood of HNSCC patients. To assess if these CD34( +) cells could differentiate into dendritic cells, they were isolated from the blood of HNSCC patients and cultured for 12 days with various cytokine combinations. Culturing CD34(+) cells with stem cell factor (c-kit ligand) plus granulocyte-macrophage colony-stimulating factor r esulted in the appearance of a significant proportion of cells express ing phenotypic markers characteristic of dendritic cells. Also, includ ing tumor necrosis factor-alpha yielded a significant proportion of ce lls resembling the bi-potential precursor cells for dendritic cells an d monocytes (CD14(+)CD1a(+)), in addition to the dendritic-like cells. When the differentiation inducer 1 alpha,25-dihydroxyvitamin D-3 [1,2 5(OH)(2)D-3] was added along with the cytokine combinations, the yield of cells having characteristics of dendritic cells was further increa sed. Cells that were derived from CD34(+) cell cultures containing 1,2 5(OH)(2)D-3 had a more potent capacity to present the recall antigen t etanus toxoid to autologous peripheral blood leukocytes and to stimula te a mixed leukocyte response compared to cultures to which 1,25(OH)2D , had not been added. Our results show that CD34(+) cells, whose frequ ency is increased in HNSCC patients, can be differentiated into cells that phenotypically and functionally resemble dendritic cells and that 1,25(OH)(2)D-3 accentuates this differentiation. (C) 1997 Wiley-Liss, Inc.