DENDRITIC ANTIGEN-PRESENTING CELLS FROM THE PERIPHERAL-BLOOD OF RENAL-CELL-CARCINOMA PATIENTS

Dendritic cells are considered to be the initiators of immune response s, including those directed against tumors. Clinical research on dendr itic cells was long hampered by the limited availability of these cell s. The recent identification of cytokine combinations that mobilize de ndritic cells with potent antigen-presenting cell function from periph eral blood represented a major progress. We show in this study that su bstantial numbers of dendritic cells can be obtained from the peripher al blood of patients with renal-cell carcinoma. The procedure requires a relatively small blood sample (40 ml) and avoids both priming of th e patient with granulocyte-colony stimulating factor and leukapheresis . Approximately 2 to 8 million cells with the characteristics of dendr itic cells could be obtained: phase-contrast microscopy revealed the t ypical cytoplasmic processes or veils; phenotypic analysis confirmed e xpression of dendritic-cell-associated molecules, including MHC class II, CD1a, CD4, ICAM-1 (CD54), LFA-3 (CD58), B7-1 (CD80) and B7-2 (CD86 ), and absence of T-cell, B-cell and monocyte markers; in addition, th ese cells rapidly attached to and migrated on collagen-type-1-coated s urfaces. Interestingly, attachment was accompanied by acquisition of t he CD 14 antigen; functionally, cultured dendritic cells proved to be very potent co-stimulators of the phytohemagglutinin-induced prolifera tion of autologous tumor-infiltrating lymphocytes. The reproducible gr owth of functional dendritic cells from cancer patients is encouraging for the design of immunotherapy protocols. (C) 1995 Wiley-Liss, Inc.