CORRELATION OF CLINICAL AND IMMUNOLOGICAL PARAMETERS OF METASTATIC RENAL-CELL CARCINOMA PATIENTS UNDERGOING THERAPY WITH INTERLEUKIN-2, INTERFERON-ALPHA AND RETINOIC ACID

IFN-gamma production in whole blood cell cultures (WBCC), and TNF-rece ptor p75 (TNF-R-75) plasma levels were measured as two independent imm unological parameters in a group of 67 untreated renal cell carcinoma (RCC) patients at different clinical stages, and 40 age matched health y controls. In the blood cell cultures of the tumor patients the level s of IFN-gamma were significantly lower compared to the controls and t he values decreased with increasing tumor mass. In contrast, TNF-R-75 plasma levels were significantly higher in the tumor patients and incr eased with tumor stage. Additionally serial assessments of these param eters were studied in another group of 15 patients with advanced RCC d uring treatment with IL-2 IFN-alpha and retinoic acid according to thr ee different protocols in order to search for any correlation between the biological marker values and the clinical response to treatment Du ring each 5 day cycle of high dose IL-2/IFN-alpha combination therapy (protocol 1) IFN-gamma-levels in the WBCC were markedly decreased, whe reas the plasma levels of TNF-R-75 were increased. During low dose, lo ng-term continuous IFN-alpha/IL-2 administration (protocol 2) in two p atients a clear increase of the ex vivo leukocyte IFN-gamma production was seen for the first 5 and 6 months of treatment, respectively, whi ch could be correlated to stable disease for. this time. When progress ion was diagnosed, IFN-gamma levels in the WBCC decreased. In the WBCC of the other four patients with progressive disease IFN-gamma levels were rather low throughout (<10 ng/ml) and no cleat changes were measu red. During low dose IFN-a and 13-cis-retinoic acid therapy in repetit ive weekly cycles (protocol 3) two patients had stable disease for 6 a nd 4 months respectively. In the WBCC cultures of these patients IFN-g amma production was higher during stable than during progressive disea se. The other two patients with tumor progression had a very low leuko cyte IFN-gamma production and high plasma levels of TNF-R-75. It is co ncluded that IFN-gamma levels in WBCC and TNF-R-75 plasma levels may b e useful parameters for the immunological monitoring of therapies with biological response modifiers. Low IFN-gamma values and high TNF-R-75 levels may be predictive of tumor progression and bad prognosis.