Innate immune evasion revealed in a colorectal zebrafish xenograft model
| Main Author: | |
|---|---|
| Publication Date: | 2021 |
| Other Authors: | , , , , , , , , |
| Format: | Article |
| Language: | eng |
| Source: | Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) |
| Download full: | http://hdl.handle.net/10362/125828 |
Summary: | LISBOA-01-0145-FEDER-022170 CEECIND/ 02699/2017 |
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Innate immune evasion revealed in a colorectal zebrafish xenograft modelChemistry(all)Biochemistry, Genetics and Molecular Biology(all)Physics and Astronomy(all)SDG 3 - Good Health and Well-beingLISBOA-01-0145-FEDER-022170 CEECIND/ 02699/2017Cancer 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.DCV - Departamento de Ciências da VidaUCIBIO - Applied Molecular Biosciences UnitRUNPóvoa, VandaRebelo de Almeida, CátiaMaia-Gil, MarianaSobral, DanielDomingues, MicaelaMartinez-Lopez, Mayrade Almeida Fuzeta, MiguelSilva, CarlosGrosso, Ana RitaFior, Rita2021-10-09T04:58:42Z2021-122021-12-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/125828eng2041-1723PURE: 34160976https://doi.org/10.1038/s41467-021-21421-yinfo:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2024-05-22T17:56:36Zoai:run.unl.pt:10362/125828Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-28T17:27:42.995913Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse |
| dc.title.none.fl_str_mv |
Innate immune evasion revealed in a colorectal zebrafish xenograft model |
| title |
Innate immune evasion revealed in a colorectal zebrafish xenograft model |
| spellingShingle |
Innate immune evasion revealed in a colorectal zebrafish xenograft model Póvoa, Vanda Chemistry(all) Biochemistry, Genetics and Molecular Biology(all) Physics and Astronomy(all) SDG 3 - Good Health and Well-being |
| title_short |
Innate immune evasion revealed in a colorectal zebrafish xenograft model |
| title_full |
Innate immune evasion revealed in a colorectal zebrafish xenograft model |
| title_fullStr |
Innate immune evasion revealed in a colorectal zebrafish xenograft model |
| title_full_unstemmed |
Innate immune evasion revealed in a colorectal zebrafish xenograft model |
| title_sort |
Innate immune evasion revealed in a colorectal zebrafish xenograft model |
| author |
Póvoa, Vanda |
| author_facet |
Póvoa, Vanda Rebelo de Almeida, Cátia Maia-Gil, Mariana Sobral, Daniel Domingues, Micaela Martinez-Lopez, Mayra de Almeida Fuzeta, Miguel Silva, Carlos Grosso, Ana Rita Fior, Rita |
| author_role |
author |
| author2 |
Rebelo de Almeida, Cátia Maia-Gil, Mariana Sobral, Daniel Domingues, Micaela Martinez-Lopez, Mayra de Almeida Fuzeta, Miguel Silva, Carlos Grosso, Ana Rita Fior, Rita |
| author2_role |
author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
DCV - Departamento de Ciências da Vida UCIBIO - Applied Molecular Biosciences Unit RUN |
| dc.contributor.author.fl_str_mv |
Póvoa, Vanda Rebelo de Almeida, Cátia Maia-Gil, Mariana Sobral, Daniel Domingues, Micaela Martinez-Lopez, Mayra de Almeida Fuzeta, Miguel Silva, Carlos Grosso, Ana Rita Fior, Rita |
| dc.subject.por.fl_str_mv |
Chemistry(all) Biochemistry, Genetics and Molecular Biology(all) Physics and Astronomy(all) SDG 3 - Good Health and Well-being |
| topic |
Chemistry(all) Biochemistry, Genetics and Molecular Biology(all) Physics and Astronomy(all) SDG 3 - Good Health and Well-being |
| description |
LISBOA-01-0145-FEDER-022170 CEECIND/ 02699/2017 |
| publishDate |
2021 |
| dc.date.none.fl_str_mv |
2021-10-09T04:58:42Z 2021-12 2021-12-01T00:00:00Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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http://hdl.handle.net/10362/125828 |
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http://hdl.handle.net/10362/125828 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
2041-1723 PURE: 34160976 https://doi.org/10.1038/s41467-021-21421-y |
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info:eu-repo/semantics/openAccess |
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openAccess |
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