NK CELLS IN TUMOR INFILTRATING LYMPHOCYTES

肿瘤浸润淋巴细胞中的 NK 细胞

• 批准号: 3187166
• 负责人: SIDNEY H GOLUB
• 金额: $ 14.98万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-05-01 至 1990-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3187166
• 关键词: antibody dependent killer cell; neoplasm /cancer immunology

The tumor infiltrating lymphocytes (TIL) of human pulmonary tumors represent both a failure of the immune system and an opportunity for the recruitment of an anti-tumor effector system. We have shown that TIL have impaired NK activity that may be due to a deficit in recycling capacity. We now propose to examine the nature of the cytolytic defect in TIL NK cells. We will determine the phase of the cytotoxic reaction (binding, programming for lysis, or killer cell independent lysis) that is impaired in TIL. The kinetics of cytotoxicity under non-recycling conditions will be determined and the production of NK cytotoxic factor (NKCF) will be tested. The possible involvement of suppressor cells in the development of cytotoxic cells will be tested by the admixture of TIL to PBL responding to IL-2. The suppression of the acquisition of Tac and transferrin receptor, and the function, will be measured. The augmentation of TIL NK activity by IL-2 wil studied. IL-2 treated TIL do develop cytotoxic activity and we will determine the optimal conditions (including the role of IL-1, prostaglandin synthesis inhibitors such as indomethancin, and gamma-IFN) for IL-2 induction of cytotoxicity. Patients will be treated with IL-2 or with IL-2 plus LAK cells prior to surgery for pulmonary malignancy. The TIL will be extracted from these tumors and the cytotoxic function and activation marker expression determined. Collectively, these studies may identify better means of using the lymphoid population that is already physically closest to the tumor cells. Restoration of immune function to these cells may result in better control of tumor growth or spread.

人肺肿瘤的肿瘤浸润性淋巴细胞（TIL）代表了 这既是免疫系统的失败，也是招募新成员的机会， 一个抗肿瘤效应系统。 我们已经证明TIL损害NK细胞， 这可能是由于回收能力不足造成的。 我们现建议 以检查TIL NK细胞中溶细胞缺陷的性质。 我们将 确定细胞毒性反应的阶段（结合，编程， 裂解，或杀伤细胞非依赖性裂解）。 的 将确定非循环条件下的细胞毒性动力学 并检测NK细胞毒因子（NKCF）的产生。 的 抑制细胞可能参与细胞毒性 将通过TIL与对IL-2有反应的PBL的混合物来测试细胞。 Tac和转铁蛋白受体获得的抑制， 功能，将被测量。 IL-2增强TIL NK活性， 研究了 IL-2处理的TIL确实产生细胞毒活性，我们将 确定最佳条件（包括IL-1、前列腺素 合成抑制剂，如吲哚美辛和γ-IFN 诱导细胞毒性。 患者将接受IL-2或IL-2治疗 加LAK细胞治疗肺部恶性肿瘤。 TIL将是 从这些肿瘤中提取的细胞毒功能和活化标志物 表达决心。 总的来说，这些研究可以更好地识别 使用身体上已经最接近的淋巴细胞群的方法 肿瘤细胞。 这些细胞的免疫功能恢复可能导致 更好地控制肿瘤生长或扩散。