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Circulating immune markers in advanced renal cell carcinoma during immunotherapy with interferon gamma

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Abstract

Circulating immune markers sICAM-1, sELAM-1, sMHC-I, β2-MG, sCD4 and sCD8 were evaluated prior to and during immunotherapy with biologically active doses of interferon gamma (IFN-γ) in 16 patients with advanced renal cell carcinoma (RCC) over a period of 12 months. Compared 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), progressive disease during therapy (n = 12) was associa ed with significantly (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 levels of sMHC-I among the RCC patients were significantly (P < 0.05) lower than among the controls (0.41 vs 0.8 ng/ml). sCD4 levels clearly showed the same tendency (24 vs 33 U/l). sCD8 baseline levels, by contrast, were significantly (P < 0.05) elevated (564 vs 336 U/l), reflecting either activation of the NK-cell subset or increased synthesis of CD8 + T-suppressor cells. Again, significantly (P < 0.05) higher intratherapeutic sCD8 concentrations were observable with progressive disease than with response to therapy or stable disease (721 vs 355 U/l). Interestingly, although the biologically active dose of IFN-γ was defined by an increase in β2-MG release of at least 30% within 48 h after injection, none of the other markers showed any significant alteration following IFN-γ administration, suggesting that IFN-γ in vivo does not produce changes in circulating markers of activation that 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 significance for indicating ongoing tumor progression.

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Authors and Affiliations

  1. Department of Urology, University of Vienna Medical School, Währinger Gürtel 18-20, A-1090, Vienna, Austria

    K. Höbarth, A. Hallas, G. Steiner & M. Marberger

  2. Salzburg General Hospital, Salzburg, Austria

    A. Gomahr & W. Aulitzky

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  1. K. Höbarth
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  2. A. Hallas
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  3. G. Steiner
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  4. A. Gomahr
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  5. W. Aulitzky
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  6. M. Marberger
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Höbarth, K., Hallas, A., Steiner, G. et al. Circulating immune markers in advanced renal cell carcinoma during immunotherapy with interferon gamma. Urol. Res. 24, 101–106 (1996). https://doi.org/10.1007/BF00431087

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  • DOI: https://doi.org/10.1007/BF00431087

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