Renal cell carcinoma - associated immune impairment that may interfere with the response to cytokine therapy

This prospective study was carried out to explore cytokine-related immune a lterations in 69 renal cell carcinoma patients (RCC) and to look for change s which might potentially serve as a reliable predictors of response to cyt okine-based therapy. Interleukin-2 (IL-2), its soluble receptor (sIL-2R) an d tumor necrosis factor (TNF-alpha) levels produced in vitro by PHA activat ed and intact mononuclear cells (PBMC) were determined. Concentrations of I L-2, IL-4, IL-6, sIL-2R, TNF-alpha and CRP were measured in sera. Cytokine level was evaluated by enzyme-linked immunoadsorbent assay (ELISA) and CRP was determined by means of turbidimetric method. All measurements were perf ormed in patients without any prior treatment. PHA activated PBMC of RCC patients were significantly defective in producin g IL-2 and TNF-alpha comparing to controls (p < 0.03 and p < 0.001). The di fference of sIL-2R was noted in metastatic stage only (p < 0.03). Unstimula ted PBMC manifested decrease in IL-2 (p < 0.03) and increased level of TNF- alpha in advanced disease (p < 0.02). This impairment reflected tumor size and differentiation stage. Serum concentrations of IL-2, sIL-2R and TNF-alp ha were within normal range. However, in relation to the clinical stage, si gnificantly increased serum IL-2 was noted in combined Stage I and II as co mpared to controls (p = 0.012). IL-6 and CRP showed markedly elevated level s with a significancy which allowed to distinguish samples from metastatic patients. In conclusion careful comparisons of these data with clinical course of cyt okine treated patients will disclose which of those tests may possess predi ctive power in the individual patients who are likely to respond to cytokin e-based treatment.