Neuroblastoma (NB), derived from the neural crest (NC), is the most common pediatric extracranial solid tumor. Here, we establish a platform that allows the study of human NBs in mouse-human NC chimeras. Chimeric mice were produced by injecting human NC cells carrying NB relevant oncogenes in utero into gastrulating mouse embryos. The mice developed tumors composed of a heterogenous cell population that resembled that seen in primary NBs of patients but were significantly different from homogeneous tumors formed in xenotransplantation models. The human tumors emerged in immunocompetent hosts and were extensively infiltrated by mouse cytotoxic T cells, reflecting a vigorous host anti-tumor immune response. However, the tumors blunted the immune response by inducing infiltration of regulatory T cells and expression of immune-suppressive molecules similar to escape mechanisms seen in human cancer patients. Thus, this experimental platform allows the study of human tumor initiation, progression, manifestation, and tumor-immune-system interactions in an animal model system.

神经母细胞瘤（NB）源自神经c（NC），是最常见的小儿颅外实体瘤。在这里，我们建立了一个平台，允许在小鼠-人NC嵌合体中研究人NB。嵌合小鼠是通过在子宫内注射携带NB相关致癌基因的人NC细胞而产生的转化为老鼠的胚胎。小鼠产生的肿瘤由异种细胞组成，类似于在患者原发性NB中所见，但与异种移植模型中形成的同质肿瘤显着不同。人类肿瘤出现在具有免疫功能的宿主中，并被小鼠细胞毒性T细胞广泛浸润，反映出强烈的宿主抗肿瘤免疫反应。然而，肿瘤通过诱导调节性T细胞的浸润和免疫抑制分子的表达而减弱了免疫反应，类似于人类癌症患者中所见的逃逸机制。因此，该实验平台允许在动物模型系统中研究人类肿瘤的发生，发展，表现以及肿瘤与免疫系统的相互作用。