美国麻省理工学院Rudolf Jaenisch、Stefani Spranger和哈佛医学院Rani E. George研究组合作发现小鼠-人类神经C（NC）嵌合体中人类神经母细胞瘤（NB）的形成。相关论文于2020年3月5日发表于《细胞-干细胞》杂志上。

他们建立了一个平台，可以研究小鼠-人NC嵌合体中的人神经母细胞瘤NB。嵌合小鼠是通过将子宫内携带NB相关癌基因的人NC细胞注射到胃化小鼠胚胎中而产生的。小鼠产生的肿瘤由异质细胞组成，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均质肿瘤明显不同。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、进展、表征以及肿瘤与免疫系统的相互作用。

据介绍，NB来自NC，是最常见的小儿颅外实体瘤。

附：英文原文

Title: Formation of Human Neuroblastoma in Mouse-Human Neural Crest Chimeras

Author: Malkiel A. Cohen, Shupei Zhang, Satyaki Sengupta, Haiting Ma, George W. Bell, Brendan Horton, Bandana Sharma, Rani E. George, Stefani Spranger, Rudolf Jaenisch

Issue&Volume: 2020-03-05

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

DOI: 10.1016/j.stem.2020.02.001

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30054-0