CIRCULATING IMMUNE MARKERS IN ADVANCED RENAL-CELL CARCINOMA DURING IMMUNOTHERAPY WITH INTERFERON-GAMMA

Circulating immune markers sICAM-1, sELAM-1, sMHC-1, beta(2)-MG, sCD4 and sCD8 were evaluated prior to and during immunotherapy with biologi cally active doses of interferon gamma (IFN-gamma) in 16 patients with advanced renal cell carcinoma (RCC) over a period of 12 months. Compa red to 20 healthy controls: significantly (P < 0.01) elevated baseline levels of circulating adhesion molecules sICAM-1 (mean 1166 vs 230 ng /ml) and sELAM-1 (70 vs 17 ng/ml) were found in all patients. Compared to responders (n = 2) or patients with stable disease (n = 2), progre ssive disease during therapy (n = 12) was associated with significantl y (P < 0.05) higher mean concentrations of sICAM-1 (1574 vs 962 ng/ml) and sELAM-1 (86 vs 46 ng/ml). Pretherapeutic and intratherapeutic lev els of sMHC-I among the RCC patients were significantly (P < 0.05) low er than among the controls (0.41 vs 0.8 ng/ml). sCD4 levels clearly sh owed the same tendency (24 vs 33 U/l). sCD8 baseline levels, by contra st, were significantly (P < 0.05) elevated (564 vs 336 U/l), reflectin g either activation of the NK-cell subset or increased synthesis of CD 8+ T-suppressor cells. Again, significantly (P < 0.05) higher intrathe rapeutic sCD8 concentrations were observable with progressive disease than with response to therapy or stable disease (721 vs 355 U/l). Inte restingly, although the biologically active dose of IFN-gamma was defi ned by an increase in beta(2)-MG release of at least 30% within 48 h a fter injection, none of the other markers showed any significant alter ation following IFN-gamma administration, suggesting that IFN-gamma in vivo does not produce changes in circulating markers of activation th at might be expected on the basis of its effects in vitro. The finding of significantly elevated concentrations of sICAM-1, sELAM-1 and sCD8 in the presence of low sCD4 and sMHC-I levels might be of clinical si gnificance for indicating ongoing tumor progression.