Formation of Human Neuroblastoma in Mouse-Human Neural Crest Chimeras
© 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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier BV
2021
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| Online Access: | https://hdl.handle.net/1721.1/136241 |
| _version_ | 1826215874629992448 |
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| author | Cohen, Malkiel A Zhang, Shupei Sengupta, Satyaki Ma, Haiting Bell, George W Horton, Brendan Sharma, Bandana George, Rani E Spranger, Stefani Jaenisch, Rudolf |
| author_facet | Cohen, Malkiel A Zhang, Shupei Sengupta, Satyaki Ma, Haiting Bell, George W Horton, Brendan Sharma, Bandana George, Rani E Spranger, Stefani Jaenisch, Rudolf |
| author_sort | Cohen, Malkiel A |
| collection | MIT |
| description | © 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. |
| first_indexed | 2024-09-23T16:38:25Z |
| format | Article |
| id | mit-1721.1/136241 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T16:38:25Z |
| publishDate | 2021 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1362412021-10-28T03:08:33Z Formation of Human Neuroblastoma in Mouse-Human Neural Crest Chimeras Cohen, Malkiel A Zhang, Shupei Sengupta, Satyaki Ma, Haiting Bell, George W Horton, Brendan Sharma, Bandana George, Rani E Spranger, Stefani Jaenisch, Rudolf © 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. 2021-10-27T20:34:27Z 2021-10-27T20:34:27Z 2020 2021-07-19T17:21:05Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/136241 en 10.1016/J.STEM.2020.02.001 Cell Stem Cell Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV PMC |
| spellingShingle | Cohen, Malkiel A Zhang, Shupei Sengupta, Satyaki Ma, Haiting Bell, George W Horton, Brendan Sharma, Bandana George, Rani E Spranger, Stefani Jaenisch, Rudolf Formation of Human Neuroblastoma in Mouse-Human Neural Crest Chimeras |
| title | Formation of Human Neuroblastoma in Mouse-Human Neural Crest Chimeras |
| title_full | Formation of Human Neuroblastoma in Mouse-Human Neural Crest Chimeras |
| title_fullStr | Formation of Human Neuroblastoma in Mouse-Human Neural Crest Chimeras |
| title_full_unstemmed | Formation of Human Neuroblastoma in Mouse-Human Neural Crest Chimeras |
| title_short | Formation of Human Neuroblastoma in Mouse-Human Neural Crest Chimeras |
| title_sort | formation of human neuroblastoma in mouse human neural crest chimeras |
| url | https://hdl.handle.net/1721.1/136241 |
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