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

Cell Stem Cell
Malkiel A CohenRudolf Jaenisch

Abstract

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.

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May 7, 2020·Nature Methods·Madhura Mukhopadhyay
Sep 29, 2020·Advanced Drug Delivery Reviews·Andrew S KhalilDavid J Mooney
Dec 21, 2020·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Judith WienkeJan J Molenaar
Mar 16, 2021·Frontiers in Cell and Developmental Biology·Lars CustersJarno Drost
May 1, 2021·Journal of Clinical Medicine·Roland ImleAna Banito

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