Innate immune evasion revealed in a colorectal zebrafish xenograft model.
Animals
Cell Line, Tumor
Colonic Neoplasms
/ metabolism
Colorectal Neoplasms
/ metabolism
Disease Models, Animal
Heterografts
Homeodomain Proteins
/ genetics
Humans
Immune Evasion
Immunity, Innate
Macrophages
/ metabolism
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Tumor Microenvironment
Xenograft Model Antitumor Assays
Zebrafish
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
19 02 2021
19 02 2021
Historique:
received:
06
03
2020
accepted:
26
01
2021
entrez:
20
2
2021
pubmed:
21
2
2021
medline:
12
3
2021
Statut:
epublish
Résumé
Cancer immunoediting is a dynamic process of crosstalk between tumor cells and the immune system. Herein, we explore the fast zebrafish xenograft model to investigate the innate immune contribution to this process. Using multiple breast and colorectal cancer cell lines and zAvatars, we find that some are cleared (regressors) while others engraft (progressors) in zebrafish xenografts. We focus on two human colorectal cancer cells derived from the same patient that show contrasting engraftment/clearance profiles. Using polyclonal xenografts to mimic intra-tumor heterogeneity, we demonstrate that SW620_progressors can block clearance of SW480_regressors. SW480_regressors recruit macrophages and neutrophils more efficiently than SW620_progressors; SW620_progressors however, modulate macrophages towards a pro-tumoral phenotype. Genetic and chemical suppression of myeloid cells indicates that macrophages and neutrophils play a crucial role in clearance. Single-cell-transcriptome analysis shows a fast subclonal selection, with clearance of regressor subclones associated with IFN/Notch signaling and escaper-expanded subclones with enrichment of IL10 pathway. Overall, our work opens the possibility of using zebrafish xenografts as living biomarkers of the tumor microenvironment.
Identifiants
pubmed: 33608544
doi: 10.1038/s41467-021-21421-y
pii: 10.1038/s41467-021-21421-y
pmc: PMC7895829
doi:
Substances chimiques
Homeodomain Proteins
0
RAG-1 protein
128559-51-3
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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