PUBLICATION
Innate immune evasion revealed in a colorectal zebrafish xenograft model
- Authors
- Póvoa, V., Rebelo de Almeida, C., Maia-Gil, M., Sobral, D., Domingues, M., Martinez-Lopez, M., de Almeida Fuzeta, M., Silva, C., Grosso, A.R., Fior, R.
- ID
- ZDB-PUB-210221-2
- Date
- 2021
- Source
- Nature communications 12: 1156 (Journal)
- Registered Authors
- Fior, Rita
- Keywords
- none
- MeSH Terms
-
- 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
- PubMed
- 33608544 Full text @ Nat. Commun.
Citation
Póvoa, V., Rebelo de Almeida, C., Maia-Gil, M., Sobral, D., Domingues, M., Martinez-Lopez, M., de Almeida Fuzeta, M., Silva, C., Grosso, A.R., Fior, R. (2021) Innate immune evasion revealed in a colorectal zebrafish xenograft model. Nature communications. 12:1156.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping