Immune cytokines have been shown to play important roles in regulating immune cell functions as well as neoplastic cells. Interleukin-4 (IL4), primarily known as a B-cell growth factor, can also activate and differentiate other immune cells. This cytokine has recently been shown to have immunotherapeutic benefit in tumor-bearing hosts. The present study assessed the effect on human renal cell carcinoma cell lines of recombinant IL4 alone and in combination with recombinant γ-interferon (IFN) or recombinant α-tumor necrosis factor (TNF). IL4 inhibited cell growth of all lines at 250–500 units/ml in a differential manner. Expression of IL4 receptors was demonstrated on renal cell carcinomas. Overall, IFN (500 units/ml) alone inhibited cell growth; however, TNF (500 units/ml) was not as strong an inhibitor. When IL4 was combined with IFN or TNF there was a significant augmentation of cell growth inhibition and modulation of cell morphology of the cell lines. Tumor-associated ganglioside antigens (NeuAcα2-3Galβ1-4Glcβ1-1′Cer, NeuAcα2-8Neu-Acα2-3Galβ1-4Glcβ1-1′Cer, GalNAcβ1-4(NeuAcα2-3)Galβ1-4Glc-β1-1′Cer, and GalNAcβ1-4(NeuAcα2-8NeuAcα2-3)Galβ1-4Glcβ11′Cer) HLA class I, HLA class I, HLA-DR, and β2-microglobulin on the cell surface of renal cancer lines were assessed by flow cytometry and radiometric binding assay. IL4 alone or in combination with other cytokines modulated HLA class I and HLA-DR expression. IL4 and IFN consistently enhanced NeuAcα2-8NeuAcα2-3Galβ1-4Glcβ1-1′Cer and GalNAcβ1-4(NeuAcα2-8NeuAcα2-3)Galβ1-4Glcβ1-1′Cer expression on individual cell lines. The study demonstrated that IL4 alone or in combination with other cytokines can significantly inhibit growth, and modulate the expression of surface major histocompatibility and tumor-associated antigens of renal cell carcinomas.
This study was supported by the Ben Eisenberg Fund and Public Service Grants CA 12582, CA 30647, and CA 42396.