Tumor-induced Immunosuppression

肿瘤诱导的免疫抑制

• 批准号: 6668434
• 负责人: Dan L. Longo
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6668434
• 关键词: human tissue; immunosuppression; interferon gamma; interleukin 10; interleukin 4; laboratory mouse; neoplasm /cancer; neoplasm /cancer immunology; nuclear factor kappa beta; tumor necrosis factor alpha

We initially observed, and it has been widely reproduced, that T cells from tumor-bearing hosts are defective in their signalling in response to antigen and in their function. A variety of defects are noted including defective nuclear translocation of the p65 NF-kappa B transcription factor, shortened half-lives for a number of cellular proteins such as TCR-zeta chain and signalling kinases of the src family, among others, and a deviation of the cytokine production profile toward Th2 cytokines (IL-4, IL-10) and away from Th1 cytokines (interferon- gamma, TNF). Evidence of suppression of immune function in mice in whom tumor is growing in hollow fibers in the peritoneal cavity without any cell-cell contact in the host suggest that a soluble tumor factor is responsible for the defect in cellular immunity. We have devised a method of reproducing these tumor- induced changes in normal T cells in vitro and are in the process of isolating the tumor-derived factor(s) responsible for the changes. In agreement with this finding, we are able to demonstrate the immunosuppressive properties of the pleural fluid isolated from cancer patients. We are in the process of isolating and characterizing the tumor-derived factor(s) from the pleural fluids of cancer patients.

我们最初观察到，来自荷瘤宿主的 T 细胞在响应抗原的信号传导和功能方面存在缺陷，这一结果已被广泛重复。注意到多种缺陷，包括 p65 NF-kappa B 转录因子的核易位缺陷、许多细胞蛋白（例如 TCR-zeta 链和 src 家族信号激酶等）的半衰期缩短以及偏差细胞因子产生谱向 Th2 细胞因子（IL-4、IL-10）和远离 Th1 细胞因子（干扰素-γ、TNF）的方向变化。肿瘤在腹腔中空纤维中生长且宿主体内没有任何细胞与细胞接触的小鼠中免疫功能受到抑制的证据表明，可溶性肿瘤因子是导致细胞免疫缺陷的原因。我们设计了一种在体外复制正常 T 细胞中肿瘤诱导变化的方法，并且正在分离导致这些变化的肿瘤衍生因子。与这一发现一致，我们能够证明从癌症患者身上分离的胸水具有免疫抑制特性。我们正在从癌症患者的胸水中分离和表征肿瘤衍生因子。