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NK CELLS IN TUMOR INFILTRATING LYMPHOCYTES

肿瘤浸润淋巴细胞中的 NK 细胞

基本信息

批准号：
3187167
负责人：
SIDNEY H GOLUB
金额：
$ 14.77万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
1987
资助国家：
美国
起止时间：
1987-05-01 至 1991-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3187167
关键词：
antibody dependent killer cell neoplasm /cancer immunology

项目摘要

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)代表既是免疫系统的故障，也是招募的机会一种抗肿瘤效应系统。我们已经证明，TIL已经损害了NK 可能是由于回收能力不足造成的活动。我们现在提议目的：探讨TIL-NK细胞溶细胞缺陷的性质。我们会确定细胞毒性反应的阶段(结合，编程溶解，或非杀伤细胞独立溶解)，在TIL中受损。这个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。这个抑制细胞可能参与细胞毒作用的发展细胞将通过混合TIL和PBL来测试对IL-2的反应。抑制Tac和转铁蛋白受体的获得，以及功能，将被测量。IL-2增强TIL-NK活性的实验研究学习。IL-2处理的TIL确实具有细胞毒活性，我们将确定最佳条件(包括IL-1、前列腺素的作用对IL-2的合成抑制物，如吲哚美辛和γ-干扰素诱导细胞毒性。患者将接受IL-2或IL-2治疗在肺部恶性肿瘤手术前加LAK细胞。TIL将会是从这些肿瘤中提取的细胞毒作用和激活标志物确定了表达式。总体而言，这些研究可能会发现更好的使用已经在物理上最接近的淋巴种群的方法肿瘤细胞。这些细胞的免疫功能可能会恢复更好地控制肿瘤的生长或扩散。