Hoon D S, Okun E, Banez M, Irie R F, Morton D L
John Wayne Cancer Institute, Santa Monica, California 90404.
Cancer Res. 1991 Oct 15;51(20):5687-93.
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 gamma-interferon (IFN) or recombinant alpha-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 (NeuAc alpha 2-3Gal beta 1-4Glc beta 1-1'Cer, NeuAc alpha 2-8NeuAc alpha 2-3Gal beta 1-4Glc beta 1-1'Cer, GalNAc beta 1-4 (NeuAc alpha 2-3)Gal beta 1-4Glc beta 1-1'Cer, and GalNAc beta 1-4(NeuAc alpha 2-8NeuAc alpha 2-3)Gal beta 1-4Glc beta 1-1'Cer) HLA class I, HLA-DR, and beta 2-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 NeuAc alpha 2-8NeuAc alpha 2-3Gal beta 1-4Glc beta 1-1'Cer and GalNAc beta 1-4(NeuAc alpha 2-8NeuAc alpha 2-3)Gal beta 1-4Glc beta 1-1'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.
免疫细胞因子已被证明在调节免疫细胞功能以及肿瘤细胞方面发挥重要作用。白细胞介素-4（IL4），主要作为一种B细胞生长因子为人所知，也能激活和分化其他免疫细胞。最近已证明这种细胞因子对荷瘤宿主具有免疫治疗益处。本研究评估了重组IL4单独以及与重组γ干扰素（IFN）或重组α肿瘤坏死因子（TNF）联合使用对人肾癌细胞系的影响。IL4以不同方式在250 - 500单位/毫升浓度下抑制所有细胞系的生长。在肾癌细胞上证实了IL4受体的表达。总体而言，单独使用IFN（500单位/毫升）可抑制细胞生长；然而，TNF（500单位/毫升）的抑制作用没那么强。当IL4与IFN或TNF联合使用时，细胞系的细胞生长抑制作用显著增强，且细胞形态发生改变。通过流式细胞术和放射性结合测定评估了肾癌细胞系细胞表面的肿瘤相关神经节苷脂抗原（NeuAcα2 - 3Galβ1 - 4Glcβ1 - 1'Cer、NeuAcα2 - 8NeuAcα2 - 3Galβ1 - 4Glcβ1 - 1'Cer、GalNAcβ1 - 4(NeuAcα2 - 3)Galβ1 - 4Glcβ1 - 1'Cer和GalNAcβ1 - 4(NeuAcα2 - 8NeuAcα2 - 3)Galβ1 - 4Glcβ1 - 1'Cer）、HLA - I类、HLA - DR和β2 - 微球蛋白。单独使用IL4或与其他细胞因子联合使用可调节HLA - I类和HLA - DR的表达。IL4和IFN持续增强单个细胞系上NeuAcα2 - 8NeuAcα2 - 3Galβ1 - 4Glcβ1 - 1'Cer和GalNAcβ1 - 4(NeuAcα2 - 8NeuAcα2 - 3)Galβ1 - 4Glcβ1 - 1'Cer的表达。该研究表明，单独使用IL4或与其他细胞因子联合使用可显著抑制肾癌细胞的生长，并调节其表面主要组织相容性和肿瘤相关抗原的表达。
