Street Shayna E A, Trapani Joseph A, MacGregor Duncan, Smyth Mark J
Cancer Immunology Program, Trescowthick Laboratories, Peter MacCallum Cancer Institute, East Melbourne, Victoria 8006, Australia.
J Exp Med. 2002 Jul 1;196(1):129-34. doi: 10.1084/jem.20020063.
The immunosurveillance of transformed cells by the immune system remains one of the most controversial and poorly understood areas of immunity. Gene-targeted mice have greatly aided our understanding of the key effector molecules in tumor immunity. Herein, we describe spontaneous tumor development in gene-targeted mice lacking interferon (IFN)-gamma and/or perforin (pfp), or the immunoregulatory cytokines, interleukin (IL)-12, IL-18, and tumor necrosis factor (TNF). Both IFN-gamma and pfp were critical for suppression of lymphomagenesis, however the level of protection afforded by IFN-gamma was strain specific. Lymphomas arising in IFN-gamma-deficient mice were very nonimmunogenic compared with those derived from pfp-deficient mice, suggesting a comparatively weaker immunoselection pressure by IFN-gamma. Single loss of IL-12, IL-18, or TNF was not sufficient for spontaneous tumor development. A significant incidence of late onset adenocarcinoma observed in both IFN-gamma- and pfp-deficient mice indicated that some epithelial tissues were also subject to immunosurveillance.
免疫系统对转化细胞的免疫监视仍然是免疫领域中最具争议且了解甚少的领域之一。基因靶向小鼠极大地帮助了我们对肿瘤免疫中关键效应分子的理解。在此，我们描述了缺乏干扰素（IFN）-γ和/或穿孔素（pfp），或免疫调节细胞因子白细胞介素（IL）-12、IL-18和肿瘤坏死因子（TNF）的基因靶向小鼠中的自发肿瘤发展情况。IFN-γ和pfp对抑制淋巴瘤发生都至关重要，然而IFN-γ提供的保护水平具有品系特异性。与源自pfp缺陷小鼠的淋巴瘤相比，IFN-γ缺陷小鼠中出现的淋巴瘤免疫原性非常低，这表明IFN-γ的免疫选择压力相对较弱。单独缺失IL-12、IL-18或TNF不足以导致自发肿瘤发展。在IFN-γ和pfp缺陷小鼠中均观察到显著发生率的迟发性腺癌，这表明一些上皮组织也受到免疫监视。
