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Of Mice, Dogs, Pigs, and Men: Choosing the Appropriate Model for Immuno-Oncology Research.
ILAR Journal ( IF 2.5 ) Pub Date : 2018-11-27 , DOI: 10.1093/ilar/ily014
Nana H Overgaard 1 , Timothy M Fan 2 , Kyle M Schachtschneider 3 , Daniel R Principe 4 , Lawrence B Schook 3, 5 , Gregers Jungersen 6
Affiliation  

The immune system plays dual roles in response to cancer. The host immune system protects against tumor formation via immunosurveillance; however, recognition of the tumor by immune cells also induces sculpting mechanisms leading to a Darwinian selection of tumor cell variants with reduced immunogenicity. Cancer immunoediting is the concept used to describe the complex interplay between tumor cells and the immune system. This concept, commonly referred to as the three E's, is encompassed by 3 distinct phases of elimination, equilibrium, and escape. Despite impressive results in the clinic, cancer immunotherapy still has room for improvement as many patients remain unresponsive to therapy. Moreover, many of the preclinical results obtained in the widely used mouse models of cancer are lost in translation to human patients. To improve the success rate of immuno-oncology research and preclinical testing of immune-based anticancer therapies, using alternative animal models more closely related to humans is a promising approach. Here, we describe 2 of the major alternative model systems: canine (spontaneous) and porcine (experimental) cancer models. Although dogs display a high rate of spontaneous tumor formation, an increased number of genetically modified porcine models exist. We suggest that the optimal immuno-oncology model may depend on the stage of cancer immunoediting in question. In particular, the spontaneous canine tumor models provide a unique platform for evaluating therapies aimed at the escape phase of cancer, while genetically engineered swine allow for elucidation of tumor-immune cell interactions especially during the phases of elimination and equilibrium.

中文翻译:

对小鼠,狗,猪和人:为免疫肿瘤学研究选择合适的模型。

免疫系统在应对癌症方面起着双重作用。宿主免疫系统可通过免疫监视防止肿瘤形成。然而,免疫细胞对肿瘤的识别也诱导了雕刻机制,导致达尔文选择了具有降低的免疫原性的肿瘤细胞变体。癌症免疫编辑是用来描述肿瘤细胞与免疫系统之间复杂相互作用的概念。这个概念通常称为三个E,由消除,平衡和逃逸的3个不同阶段涵盖。尽管在临床上取得了令人瞩目的成果,但由于许多患者仍对治疗无反应,因此癌症免疫疗法仍有改善的空间。而且,在广泛使用的癌症小鼠模型中获得的许多临床前结果在翻译给人类患者时丢失了。为了提高免疫肿瘤学研究和基于免疫的抗癌疗法的临床前测试的成功率,使用与人类更紧密相关的替代动物模型是一种有前途的方法。在这里,我们描述了两种主要的替代模型系统:犬(自发性)和猪(实验性)癌症模型。尽管狗表现出很高的自发肿瘤形成率,但是存在数量增加的转基因猪模型。我们建议最佳的免疫肿瘤学模型可能取决于所讨论的癌症免疫编辑的阶段。特别是自发的犬肿瘤模型提供了一个独特的平台,用于评估针对癌症逃逸阶段的疗法,
更新日期:2019-11-01
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