Formation of Human Neuroblastoma in Mouse-Human Neural Crest Chimeras.

Animals Child Chimera Disease Models, Animal Humans Mice Neural Crest Neuroblastoma
cancer model immune evasion interspecies chimeras neural crest neuroblastoma pluripotent stem cells

Journal

Cell stem cell
ISSN: 1875-9777
Titre abrégé: Cell Stem Cell
Pays: United States
ID NLM: 101311472

Informations de publication

Date de publication:
02 04 2020
Historique:
received: 09 01 2019
revised: 04 10 2019
accepted: 03 02 2020
pubmed: 7 3 2020
medline: 28 4 2021
entrez: 7 3 2020
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.stem.2020.02.001 PMID: 32142683 PMC: PMC7663823
pubmed: 32142683
pii: S1934-5909(20)30054-0
doi: 10.1016/j.stem.2020.02.001
pmc: PMC7663823
mid: NIHMS1622641
pii:
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

579-592.e6

Subventions

Organisme : NIMH NIH HHS
ID : R01 MH104610
Pays : United States
Organisme : NCI NIH HHS
ID : R00 CA204595
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS088538
Pays : United States
Organisme : NICHD NIH HHS
ID : R37 HD045022
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA148688
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2020. Published by Elsevier Inc.

Déclaration de conflit d'intérêts

Declaration of Interests R.J. is a cofounder of Fate Therapeutics, Fulcrum Therapeutics, and Omega Therapeutics and an advisor to Dewpoint Therapeutics.

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Auteurs

Malkiel A Cohen (MA)

Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.

Shupei Zhang (S)

Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.

Satyaki Sengupta (S)

Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.

Haiting Ma (H)

Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.

George W Bell (GW)

Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.

Brendan Horton (B)

Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.

Bandana Sharma (B)

Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.

Rani E George (RE)

Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. Electronic address: rani_george@dfci.harvard.edu.

Stefani Spranger (S)

Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA. Electronic address: spranger@mit.edu.

Rudolf Jaenisch (R)

Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA. Electronic address: jaenisch@wi.mit.edu.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Formation of Human Neuroblastoma in...
questionsmedicales.fr › Personnes › Tranches d'âge › Enfant › Formation of Human Neuroblastoma in...
questionsmedicales.fr › Stades d'organismes › Chimère › Formation of Human Neuroblastoma in...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › Formation of Human Neuroblastoma in...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Formation of Human Neuroblastoma in...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Formation of Human Neuroblastoma in...
questionsmedicales.fr › Structures de l'embryon › Crête neurale › Formation of Human Neuroblastoma in...
questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Tumeurs du tissu nerveux › Tumeurs neuroectodermiques › Tumeurs neuroépitheliales › Tumeurs neuroectodermiques primitives › Tumeurs neuroectodermiques primitives périphériques › Neuroblastome › Formation of Human Neuroblastoma in...