TY - JOUR T1 - Development of Human Neuroblastomas in Mouse-Human Neural Crest Chimeras JF - bioRxiv DO - 10.1101/523795 SP - 523795 AU - Malkiel A. Cohen AU - Shupei Zhang AU - Satyaki Sengupta AU - Haiting Ma AU - Brendan Horton AU - George W. Bell AU - Rani E. George AU - Stefani Spranger AU - Rudolf Jaenisch Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/01/18/523795.abstract N2 - 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. ER -