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A multi-organ-on-chip to recapitulate the infiltration and the cytotoxic activity of circulating NK cells in 3D matrix-based tumor model
The success of immunotherapeutic approaches strictly depends on the immune cells interaction with cancer cells. While conventional in vitro cell cultures under-represent the complexity and dynamic crosstalk of the tumor microenvironment, animal models do not allow deciphering the anti-tumor activity...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9358021/ https://www.ncbi.nlm.nih.gov/pubmed/35957642 http://dx.doi.org/10.3389/fbioe.2022.945149 |
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author | Marzagalli, Monica Pelizzoni, Giorgia Fedi, Arianna Vitale, Chiara Fontana, Fabrizio Bruno, Silvia Poggi, Alessandro Dondero, Alessandra Aiello, Maurizio Castriconi, Roberta Bottino, Cristina Scaglione, Silvia |
author_facet | Marzagalli, Monica Pelizzoni, Giorgia Fedi, Arianna Vitale, Chiara Fontana, Fabrizio Bruno, Silvia Poggi, Alessandro Dondero, Alessandra Aiello, Maurizio Castriconi, Roberta Bottino, Cristina Scaglione, Silvia |
author_sort | Marzagalli, Monica |
collection | PubMed |
description | The success of immunotherapeutic approaches strictly depends on the immune cells interaction with cancer cells. While conventional in vitro cell cultures under-represent the complexity and dynamic crosstalk of the tumor microenvironment, animal models do not allow deciphering the anti-tumor activity of the human immune system. Therefore, the development of reliable and predictive preclinical models has become crucial for the screening of immune-therapeutic approaches. We here present an organ-on-chip organ on chips (OOC)-based approach for recapitulating the immune cell Natural Killer (NK) migration under physiological fluid flow, infiltration within a 3D tumor matrix, and activation against neuroblastoma cancer cells in a humanized, fluid-dynamic environment. Circulating NK cells actively initiate a spontaneous “extravasation” process toward the physically separated tumor niche, retaining their ability to interact with matrix-embedded tumor cells, and to display a cytotoxic effect (tumor cell apoptosis). Since NK cells infiltration and phenotype is correlated with prognosis and response to immunotherapy, their phenotype is also investigated: most importantly, a clear decrease in CD16-positive NK cells within the migrated and infiltrated population is observed. The proposed immune-tumor OOC-based model represents a promising approach for faithfully recapitulating the human pathology and efficiently employing the immunotherapies testing, eventually in a personalized perspective. An immune-organ on chip to recapitulate the tumor-mediated infiltration of circulating immune cells within 3D tumor model. |
format | Online Article Text |
id | pubmed-9358021 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93580212022-08-10 A multi-organ-on-chip to recapitulate the infiltration and the cytotoxic activity of circulating NK cells in 3D matrix-based tumor model Marzagalli, Monica Pelizzoni, Giorgia Fedi, Arianna Vitale, Chiara Fontana, Fabrizio Bruno, Silvia Poggi, Alessandro Dondero, Alessandra Aiello, Maurizio Castriconi, Roberta Bottino, Cristina Scaglione, Silvia Front Bioeng Biotechnol Bioengineering and Biotechnology The success of immunotherapeutic approaches strictly depends on the immune cells interaction with cancer cells. While conventional in vitro cell cultures under-represent the complexity and dynamic crosstalk of the tumor microenvironment, animal models do not allow deciphering the anti-tumor activity of the human immune system. Therefore, the development of reliable and predictive preclinical models has become crucial for the screening of immune-therapeutic approaches. We here present an organ-on-chip organ on chips (OOC)-based approach for recapitulating the immune cell Natural Killer (NK) migration under physiological fluid flow, infiltration within a 3D tumor matrix, and activation against neuroblastoma cancer cells in a humanized, fluid-dynamic environment. Circulating NK cells actively initiate a spontaneous “extravasation” process toward the physically separated tumor niche, retaining their ability to interact with matrix-embedded tumor cells, and to display a cytotoxic effect (tumor cell apoptosis). Since NK cells infiltration and phenotype is correlated with prognosis and response to immunotherapy, their phenotype is also investigated: most importantly, a clear decrease in CD16-positive NK cells within the migrated and infiltrated population is observed. The proposed immune-tumor OOC-based model represents a promising approach for faithfully recapitulating the human pathology and efficiently employing the immunotherapies testing, eventually in a personalized perspective. An immune-organ on chip to recapitulate the tumor-mediated infiltration of circulating immune cells within 3D tumor model. Frontiers Media S.A. 2022-07-25 /pmc/articles/PMC9358021/ /pubmed/35957642 http://dx.doi.org/10.3389/fbioe.2022.945149 Text en Copyright © 2022 Marzagalli, Pelizzoni, Fedi, Vitale, Fontana, Bruno, Poggi, Dondero, Aiello, Castriconi, Bottino and Scaglione. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Bioengineering and Biotechnology Marzagalli, Monica Pelizzoni, Giorgia Fedi, Arianna Vitale, Chiara Fontana, Fabrizio Bruno, Silvia Poggi, Alessandro Dondero, Alessandra Aiello, Maurizio Castriconi, Roberta Bottino, Cristina Scaglione, Silvia A multi-organ-on-chip to recapitulate the infiltration and the cytotoxic activity of circulating NK cells in 3D matrix-based tumor model |
title | A multi-organ-on-chip to recapitulate the infiltration and the cytotoxic activity of circulating NK cells in 3D matrix-based tumor model |
title_full | A multi-organ-on-chip to recapitulate the infiltration and the cytotoxic activity of circulating NK cells in 3D matrix-based tumor model |
title_fullStr | A multi-organ-on-chip to recapitulate the infiltration and the cytotoxic activity of circulating NK cells in 3D matrix-based tumor model |
title_full_unstemmed | A multi-organ-on-chip to recapitulate the infiltration and the cytotoxic activity of circulating NK cells in 3D matrix-based tumor model |
title_short | A multi-organ-on-chip to recapitulate the infiltration and the cytotoxic activity of circulating NK cells in 3D matrix-based tumor model |
title_sort | multi-organ-on-chip to recapitulate the infiltration and the cytotoxic activity of circulating nk cells in 3d matrix-based tumor model |
topic | Bioengineering and Biotechnology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9358021/ https://www.ncbi.nlm.nih.gov/pubmed/35957642 http://dx.doi.org/10.3389/fbioe.2022.945149 |
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