Cavallo Federica, Offringa Rienk, van der Burg Sjoerd H, Forni Guido, Melief Cornelis J M
Department of Clinical and Biological Sciences, University of Torino, Torino, Italy.
Adv Immunol. 2006;90:175-213. doi: 10.1016/S0065-2776(06)90005-4.
Two approaches to immunological intervention in tumor-host interactions in mouse models are discussed in this review. The first is described with reference to experiments in which CD8(+) T lymphocytes are used to kill established transplantable tumors. Peptides and their optimal presentation by dendritic cells and intervention in immune regulatory mechanisms are the key issues for efficient induction of T-killer cell-mediated tumor eradication. The time frame of tumor therapy and the threat imposed by tumor growth in transplantable models and cancer patients require the induction of a robust T-cell reaction. Prevention of the progression of small preneoplastic lesions, on the other hand, requires the significant and prolonged immune protection sought in the second approach. This is based on antibody production and the coordinated activation of multiple low-avidity cell-mediated mechanisms elicited by DNA vaccination in genetically modified cancer-prone mice, transgenic for a mutant Her-2/neu growth factor receptor expressed at the plasma membrane surface of preneoplastic mammary gland epithelial cells. Vaccination with appropriate DNA formulations results in prolonged immune inhibition of the progression of preneoplastic mammary lesions but is ineffective against established tumors. The use of molecularly defined adjuvants and intervention in immune regulatory mechanisms are critical in both the elicitation of an effective T-cell mediated reaction required for tumor debulking in the first set of models and the induction by vaccination of a sustained immune memory able to prevent the expansion of preneoplastic lesions in genetically cancer-prone mice.
本综述讨论了小鼠模型中肿瘤-宿主相互作用的两种免疫干预方法。第一种方法参考了使用CD8(+) T淋巴细胞杀死已建立的可移植肿瘤的实验进行描述。肽及其由树突状细胞的最佳呈递以及对免疫调节机制的干预是有效诱导T杀伤细胞介导的肿瘤根除的关键问题。肿瘤治疗的时间框架以及可移植模型和癌症患者中肿瘤生长带来的威胁需要诱导强烈的T细胞反应。另一方面，预防小的癌前病变进展需要第二种方法中所寻求的显著且持久的免疫保护。这基于抗体产生以及在转基因的易患癌症小鼠中通过DNA疫苗接种引发的多种低亲和力细胞介导机制的协同激活，这些小鼠在癌前乳腺上皮细胞质膜表面表达突变的Her-2/neu生长因子受体。用适当的DNA制剂进行疫苗接种可长期免疫抑制癌前乳腺病变的进展，但对已建立的肿瘤无效。在第一组模型中，使用分子定义的佐剂和对免疫调节机制的干预对于引发肿瘤消减所需的有效T细胞介导反应至关重要，而在转基因易患癌症小鼠中，通过疫苗接种诱导能够预防癌前病变扩展的持续免疫记忆也至关重要。
