IMMUNITY AND TUMOR PROGRESSION SYSTEM

恶性生长增加的可遗传变异的研究进展 潜在性是肿瘤进展的标志，也是 癌症的治疗失败和致命性。紫外线诱导的小鼠回归模型 肿瘤在裸鼠体内生长，但在正常小鼠体内无法生长，因此 展示了免疫系统在预防疾病方面的非凡能力 癌症生长。然而，阻遏物肿瘤的变异细胞可以逃脱 强烈的免疫抑制。长远目标是： 确定这些变异肿瘤逃逸的机制，以便 能够逆转或阻止这一过程。各种参数，T细胞， 细胞因子和癌基因/抑制基因通过不同的机制发挥作用 都可能参与防止免疫排斥反应的共同途径或 增强免疫活性宿主体内肿瘤的生长。 最近，一大批紫外线诱导的小鼠肿瘤被衍生为 这些研究。银行里有一对近乎匹配的父母 退行性肿瘤、同一肿瘤的进展性变种和自体肿瘤 来自肿瘤起源的小鼠的非恶性细胞和DNA。具体的 目的是：(1)确定CD8+T细胞是否发生改变 细胞对进展型变异体的反应，特别是对保留的变异体 CTL定义的肿瘤抗原；(2)确定CD4+T细胞是否 对进化子变体的发展很重要；(3)确定 转化生长因子-β和肿瘤坏死因子在肿瘤进展中的作用 细胞因子由退化子和进行子不同地产生 变异体；(4)确定某些表达是否发生变化 癌基因或抑癌基因可导致或阻止肿瘤逃逸T细胞 依赖细胞的免疫破坏；以及(5)寻找基因 在允许肿瘤进展的步骤期间开/上或关/下 进展性肿瘤逃避正常的宿主免疫。

The development of heritable variants with increased malignant growth potential is the hallmark of tumor progression and a major reason for therapeutic failure and lethality of cancer. Murine UV-induced regressor tumors grow in nude but fail to grow in normal mice, thereby demonstrating the remarkable power of the immune system in preventing cancer growth. However, variant cells of repressor tumors can escape strong immunological restraints. The long-term objectives are: to determine the mechanisms by which these variant tumors escape in order to be able to reverse or prevent the process. Diverse parameters, T cells, cytokines and, onco/suppressor genes act through different mechanisms but may all participate in a common pathway that prevents immune rejection or enhances growth of the tumor in the immunocompetent host. A large bank of UV-induced murine tumors was recently derived for these studies. The bank contains closely matched pairs of parental regressor tumors, progressor variants of the same tumor, and autologous non-malignant cells and DNA from the mouse of tumor origin. The specific aims are: (1) To determine whether there is an alteration in the CD8+ T cell response to progressor variants, particularly to those that retain the CTL-defined tumor antigens; (2) To determine whether CD4+ T cells are important for the outgrowth of progressor variants; (3)To determine the role of TGF-beta and TNF in tumor progression and whether these or other cytokines are differentially produced by regressors and progressor variants; (4) To determine whether changes in the expression of certain oncogenes or suppressor genes can cause or prevent tumor escape from T cell-dependent immune destruction; and (5) To search for genes turned on/up or turned off/down during the step of tumor progression that allows progressor tumors to escape normal host immunity.