IMMUNITY AND TUMOR PROGRESSION SYSTEM

恶性生长增加的遗传变异的发展 潜力是肿瘤进展的标志， 癌症的治疗失败和致命性。 小鼠紫外线诱导回归因子 肿瘤在裸鼠中生长，但在正常小鼠中不能生长， 证明了免疫系统在预防 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。 长期目标是： 确定这些变异肿瘤逃逸的机制， 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起作用， 可能都参与了一个共同的途径，防止免疫排斥反应， 增强肿瘤在免疫活性宿主中的生长。 最近，一个大型的紫外线诱导的小鼠肿瘤库被用于 这些研究。 这个银行包含了非常匹配的父母对， 消退肿瘤、同一肿瘤的进展变体和自体 非恶性细胞和来自肿瘤来源的小鼠的DNA。 具体 目的是：（1）确定是否有CD 8 + T细胞的改变， 细胞对进展因子变异体的反应，特别是对那些保留 CTL定义的肿瘤抗原;（2）确定CD 4 + T细胞是否 重要的进展变异的产物;（3）为了确定 TGF-β和TNF在肿瘤进展中的作用，以及这些或其他 细胞因子由退化者和进展者不同地产生， （4）确定某些表达的变化 癌基因或抑癌基因可以导致或阻止肿瘤从T细胞逃逸， 细胞依赖性免疫破坏;（5）寻找基因， 在肿瘤进展的步骤期间打开/打开或关闭/关闭， 进展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.