Innate immune evasion revealed in a colorectal zebrafish xenograft model

Vanda Póvoa, Cátia Rebelo de Almeida, Mariana Maia-Gil, Daniel Sobral, Micaela Domingues, Mayra Martinez-Lopez, Miguel de Almeida Fuzeta, Carlos Silva, Ana Rita Grosso and Rita Fior ()
Additional contact information
Vanda Póvoa: Champalimaud Foundation
Cátia Rebelo de Almeida: Champalimaud Foundation
Mariana Maia-Gil: Champalimaud Foundation
Daniel Sobral: Universidade NOVA de Lisboa
Micaela Domingues: Champalimaud Foundation
Mayra Martinez-Lopez: Champalimaud Foundation
Miguel de Almeida Fuzeta: Champalimaud Foundation
Carlos Silva: Champalimaud Foundation
Ana Rita Grosso: Universidade NOVA de Lisboa
Rita Fior: Champalimaud Foundation

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: Abstract 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.

Date: 2021
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-21421-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21421-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-21421-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().