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-receptor p75 (TNF-R-75) plasma levels were measured as two independent immunological parameters in a group of 67 untreated renal cell carcinoma (RCC) patients at different clinical stages, and 40 age matched healthy controls. In the blood cell cultures of the tumor patients the levels of IFN-gamma were significantly lower compared to the controls and the values decreased with increasing tumor mass. In contrast, TNF-R-75 plasma levels were significantly higher in the tumor patients and increased with tumor stage. Additionally serial assessments of these parameters were studied in another group of 15 patients with advanced RCC during treatment with IL-2, IFN-alpha and retinoic acid according to three different protocols in order to search for any correlation between the biological marker values and the clinical response to treatment. During each 5 day cycle of high dose IL-2/IFN-alpha combination therapy (protocol 1) IFN-gamma-levels in the WBCC were markedly decreased, whereas the plasma levels of TNF-R-75 were increased. During low dose, long-term continuous IFN-alpha/IL-2 administration (protocol 2) in two patients a clear increase of the ex vivo leukocyte IFN-gamma production was seen for the first 5 and 6 months of treatment, respectively, which could be correlated to stable disease for this time. When progression was diagnosed, IFN-gamma levels in the WBCC decreased. In the WBCC of the other four patients with progressive IFN-gamma levels were rather low throughout (< 10 ng/ml) and no clear changes were measured. During low does IFN-alpha and 13-cis-retinoic acid therapy in repetitive weekly cycles (protocol 3) two patients had stable disease for 6 and 14 months respectively. In the WBCC cultures of these patients IFN-gamma production was higher during stable than during progressive disease. The other two patients with tumor progression had a very low leukocyte IFN-gamma production and high plasma levels of TNF-R-75. It is concluded that IFN-gamma levels in WBCC and TNF-R-75 plasma levels may be 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.