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The tumour microenvironment shapes dendritic cell plasticity in a human organotypic melanoma culture
The tumour microenvironment (TME) forms a major obstacle in effective cancer treatment and for clinical success of immunotherapy. Conventional co-cultures have shed light onto multiple aspects of cancer immunobiology, but they are limited by the lack of physiological complexity. We develop a human o...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265463/ https://www.ncbi.nlm.nih.gov/pubmed/32488012 http://dx.doi.org/10.1038/s41467-020-16583-0 |
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author | Di Blasio, S. van Wigcheren, G. F. Becker, A. van Duffelen, A. Gorris, M. Verrijp, K. Stefanini, I. Bakker, G. J. Bloemendal, M. Halilovic, A. Vasaturo, A. Bakdash, G. Hato, S. V. de Wilt, J. H. W. Schalkwijk, J. de Vries, I. J. M. Textor, J. C. van den Bogaard, E. H. Tazzari, M. Figdor, C. G. |
author_facet | Di Blasio, S. van Wigcheren, G. F. Becker, A. van Duffelen, A. Gorris, M. Verrijp, K. Stefanini, I. Bakker, G. J. Bloemendal, M. Halilovic, A. Vasaturo, A. Bakdash, G. Hato, S. V. de Wilt, J. H. W. Schalkwijk, J. de Vries, I. J. M. Textor, J. C. van den Bogaard, E. H. Tazzari, M. Figdor, C. G. |
author_sort | Di Blasio, S. |
collection | PubMed |
description | The tumour microenvironment (TME) forms a major obstacle in effective cancer treatment and for clinical success of immunotherapy. Conventional co-cultures have shed light onto multiple aspects of cancer immunobiology, but they are limited by the lack of physiological complexity. We develop a human organotypic skin melanoma culture (OMC) that allows real-time study of host-malignant cell interactions within a multicellular tissue architecture. By co-culturing decellularized dermis with keratinocytes, fibroblasts and immune cells in the presence of melanoma cells, we generate a reconstructed TME that closely resembles tumour growth as observed in human lesions and supports cell survival and function. We demonstrate that the OMC is suitable and outperforms conventional 2D co-cultures for the study of TME-imprinting mechanisms. Within the OMC, we observe the tumour-driven conversion of cDC2s into CD14(+) DCs, characterized by an immunosuppressive phenotype. The OMC provides a valuable approach to study how a TME affects the immune system. |
format | Online Article Text |
id | pubmed-7265463 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-72654632020-06-12 The tumour microenvironment shapes dendritic cell plasticity in a human organotypic melanoma culture Di Blasio, S. van Wigcheren, G. F. Becker, A. van Duffelen, A. Gorris, M. Verrijp, K. Stefanini, I. Bakker, G. J. Bloemendal, M. Halilovic, A. Vasaturo, A. Bakdash, G. Hato, S. V. de Wilt, J. H. W. Schalkwijk, J. de Vries, I. J. M. Textor, J. C. van den Bogaard, E. H. Tazzari, M. Figdor, C. G. Nat Commun Article The tumour microenvironment (TME) forms a major obstacle in effective cancer treatment and for clinical success of immunotherapy. Conventional co-cultures have shed light onto multiple aspects of cancer immunobiology, but they are limited by the lack of physiological complexity. We develop a human organotypic skin melanoma culture (OMC) that allows real-time study of host-malignant cell interactions within a multicellular tissue architecture. By co-culturing decellularized dermis with keratinocytes, fibroblasts and immune cells in the presence of melanoma cells, we generate a reconstructed TME that closely resembles tumour growth as observed in human lesions and supports cell survival and function. We demonstrate that the OMC is suitable and outperforms conventional 2D co-cultures for the study of TME-imprinting mechanisms. Within the OMC, we observe the tumour-driven conversion of cDC2s into CD14(+) DCs, characterized by an immunosuppressive phenotype. The OMC provides a valuable approach to study how a TME affects the immune system. Nature Publishing Group UK 2020-06-02 /pmc/articles/PMC7265463/ /pubmed/32488012 http://dx.doi.org/10.1038/s41467-020-16583-0 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Di Blasio, S. van Wigcheren, G. F. Becker, A. van Duffelen, A. Gorris, M. Verrijp, K. Stefanini, I. Bakker, G. J. Bloemendal, M. Halilovic, A. Vasaturo, A. Bakdash, G. Hato, S. V. de Wilt, J. H. W. Schalkwijk, J. de Vries, I. J. M. Textor, J. C. van den Bogaard, E. H. Tazzari, M. Figdor, C. G. The tumour microenvironment shapes dendritic cell plasticity in a human organotypic melanoma culture |
title | The tumour microenvironment shapes dendritic cell plasticity in a human organotypic melanoma culture |
title_full | The tumour microenvironment shapes dendritic cell plasticity in a human organotypic melanoma culture |
title_fullStr | The tumour microenvironment shapes dendritic cell plasticity in a human organotypic melanoma culture |
title_full_unstemmed | The tumour microenvironment shapes dendritic cell plasticity in a human organotypic melanoma culture |
title_short | The tumour microenvironment shapes dendritic cell plasticity in a human organotypic melanoma culture |
title_sort | tumour microenvironment shapes dendritic cell plasticity in a human organotypic melanoma culture |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265463/ https://www.ncbi.nlm.nih.gov/pubmed/32488012 http://dx.doi.org/10.1038/s41467-020-16583-0 |
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