ACTIVATION OF CYTOLYTIC ACTIVITY IN PERIPHERAL-BLOOD MONOCYTES OF RENAL-CANCER PATIENTS AGAINST NONCULTURED AUTOLOGOUS TUMOR-CELLS

Our purpose was to evaluate the ability of blood monocytes of renal ca ncer patients to become cytotoxic against fresh, autologous tumor cell s. Fresh target cells were obtained by mechanical and enzymatic dissoc iation of tumor and normal renal tissue. The A375 cell line, derived f rom a human melanoma, and the SW626 cell line, derived from a human ov arian carcinoma, were used as positive target cell controls. Monocytes from renal cancer patients and normal volunteers were activated in vi tro with lipopolysaccharide (LPS), or muramyl tripeptide (MTPPE), or m ultilamellar vesicle liposomes containing MTP-PE (MLV-MTP-PE), with or without a pre-incubation with r-IFN-gamma, and tested for cytotoxicit y in a 72-hr Indium-111-release assay. All patients were tumor-free at the time of the monocyte study. No difference in cytotoxic activity w as observed between monocytes from healthy volunteers and those from c ancer patients. Freshly dissociated tumor cells were as susceptible to tumoricidal monocytes as the 2 cell lines. Moreover, no cell populati on appeared to be resistant to activated monocytes, which were cytotox ic to both allogeneic and autologous fresh tumor cells. Activated mono cytes maintained their ability to discriminate between normal and neop lastic cells and were not cytotoxic against autologous or allogeneic n ormal non-neoplastic cells. Our data indicate that MLV MTP-PE liposome s activate peripheral blood monocytes from cancer patients to a tumori cidal status against fresh, dissociated non-cultured autologous tumor cells. (C) 1993 Wiley-Liss, Inc.