Development of Human Neuroblastomas in Mouse-Human Neural Crest Chimeras
Development of Human Neuroblastomas in Mouse-Human Neural Crest Chimeras
Summary Neuroblastoma (NB), derived from the neural crest (NC), is the most common pediatric extracranial solid tumor. Here we establish a platform that allows studying 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 closely resembled that seen in primary NBs of patients but were significantly different from homogenous 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 checkpoints similar to escape mechanisms seen in human cancer patients. Thus, this experimental platform allows studying human tumor initiation, progression, manifestation and tumor – immune-system interactions in an animal model system.
Ma Haiting、Cohen Malkiel A.、Bell George W.、Horton Brendan、Spranger Stefani、George Rani E.、Sengupta Satyaki、Zhang Shupei、Jaenisch Rudolf
Whitehead Institute for Biomedical ResearchWhitehead Institute for Biomedical ResearchWhitehead Institute for Biomedical ResearchKoch Institute for Integrative Cancer Research, Massachusetts Institute of TechnologyKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology||Department of Biology, Massachusetts Institute of TechnologyDana-Farber Cancer Institute, Harvard Medical SchoolDana-Farber Cancer Institute, Harvard Medical SchoolWhitehead Institute for Biomedical ResearchWhitehead Institute for Biomedical Research||Department of Biology, Massachusetts Institute of Technology
肿瘤学基础医学神经病学、精神病学
Interspecies ChimerasNeuroblastomaNeural CrestCancer ModelPluripotent Stem Cells
Ma Haiting,Cohen Malkiel A.,Bell George W.,Horton Brendan,Spranger Stefani,George Rani E.,Sengupta Satyaki,Zhang Shupei,Jaenisch Rudolf.Development of Human Neuroblastomas in Mouse-Human Neural Crest Chimeras[EB/OL].(2025-03-28)[2025-06-07].https://www.biorxiv.org/content/10.1101/523795.点此复制
评论