IL-4 RECEPTORS ON MURINE SOLID TUMORS AND TUMOR INFILTRATING LYMPHOCYTES

我们以前曾报道过白细胞介素-4受体的存在 （IL-4 R）对甲基胆蒽（MCA-106、MCA-102和MC-38）和病毒DNA的影响 （G-2 TS和14- 2 TS）诱导的鼠肉瘤细胞。 这些受体是 其特征类似于我们在TIL细胞上观察到特征， 其它作用于T和B淋巴细胞、肥大细胞和巨噬细胞。 这些 受体在与嵌合蛋白结合后内化， IL-4和假单胞菌外毒素（IL-4-PE 40）。 使用IL-4PE 40，我们观察到 IL-4-PE 40具有细胞毒性（通过抑制蛋白质 通过[（3）H]-亮氨酸摄取合成）以一定剂量对MCA-106肿瘤细胞的作用 依赖的方式。 IL-4-PE 40 asp（553），一种嵌合突变蛋白， 可结合IL-4受体，但不具有抑制 蛋白质合成对肿瘤细胞没有细胞毒性。 这些研究 表明当小鼠MCA-106肉瘤细胞上IL-4 R被内化时， 被IL-4-PE 40占据并且可能是功能性的。这些数据加在一起 提示IL-4受体可能是IL-4毒素治疗靶点。 目前我们已经发现TNF-α上调肿瘤细胞表面IL-4受体， 细胞 我们正在积极开展研究， IL-4受体表达增强的机制和可能作用 肿瘤细胞

We have previously reported the presence of the Interleukin-4 receptor (IL-4R) on methylcholanthrene (MCA-106, MCA-102 and MC-38) and viral DNA (G-2TS and 14-2TS) induced murine sarcoma cells. These receptors are similar in characteristics to that observed by us on TIL cells and by others on T and B lymphocytes, mast cells and macrophages. These receptors are internalized after binding to a chimeric protein between IL-4 and pseudomonas exotoxin (IL-4-PE40). Using IL-4PE40, we observed that IL-4-PE40 was cytotoxic (determined by inhibition of protein synthesis by [(3)H]-Leucine uptake) to MCA-106 tumor cells in a dose dependent manner. IL-4-PE40 asp(553), a chimeric mutant protein which can bind to IL-4 receptors but does not have the capability to inhibit protein synthesis was not cytotoxic to tumor cells. These studies suggest that IL-4R on murine MCA-106 sarcoma cells is internalized when occupied by IL-4-PE40 and may be functional. taken together, these data suggest that IL-4 receptor may be a target for IL-4-toxin therapy. Now we have found that TNF-alpha upregulates IL-4 receptors on tumor cells. We are actively pursuing our research to investigate the mechanism and possible role of augmented expression of IL-4 receptors on tumor cells.