This is not the latest version of this item. The latest version can be found here.
Formation of Human Neuroblastoma in Mouse-Human Neural Crest Chimeras
Name
nihms-1622641.pdf
Description
Accepted version
Size
2.12 MB
Format
Adobe PDF
Checksum (MD5)
94c16417b2c36bead706314cc4bfc749
Author(s)
Cohen, Malkiel A
Zhang, Shupei
Sengupta, Satyaki
Ma, Haiting
Bell, George W
Horton, Brendan
Sharma, Bandana
George, Rani E
Spranger, Stefani
Jaenisch, Rudolf
Date Issued
2020
Journal
Cell Stem Cell
Publisher
Elsevier BV
Version
Author's final manuscript
Abstract
© 2020 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.
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
10.1016/J.STEM.2020.02.001
