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Hypoxia increases melanoma-associated fibroblasts immunosuppressive potential and inhibitory effect on T cell-mediated cytotoxicity
Cancer-associated fibroblasts (CAFs) and hypoxia are central players in the complex process of tumor cell-stroma interaction and are involved in the alteration of the anti-tumor immune response by impacting both cancer and immune cell populations. However, even if their independent immunomodulatory...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312612/ https://www.ncbi.nlm.nih.gov/pubmed/34367731 http://dx.doi.org/10.1080/2162402X.2021.1950953 |
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author | Ziani, Linda Buart, Stéphanie Chouaib, Salem Thiery, Jerome |
author_facet | Ziani, Linda Buart, Stéphanie Chouaib, Salem Thiery, Jerome |
author_sort | Ziani, Linda |
collection | PubMed |
description | Cancer-associated fibroblasts (CAFs) and hypoxia are central players in the complex process of tumor cell-stroma interaction and are involved in the alteration of the anti-tumor immune response by impacting both cancer and immune cell populations. However, even if their independent immunomodulatory properties are now well documented, whether the interaction between these two components of the tumor microenvironment can affect CAFs ability to alter the anti-tumor immune response is still poorly defined. In this study, we provide evidence that hypoxia increases melanoma-associated fibroblasts expression and/or secretion of several immunosuppressive factors (including TGF-β, IL6, IL10, VEGF and PD-L1). Moreover, we demonstrate that hypoxic CAF secretome exerts a more profound effect on T cell-mediated cytotoxicity than its normoxic counterpart. Together, our data suggest that the crosstalk between hypoxia and CAFs is probably an important determinant in the complex immunosuppressive tumor microenvironment. |
format | Online Article Text |
id | pubmed-8312612 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-83126122021-08-06 Hypoxia increases melanoma-associated fibroblasts immunosuppressive potential and inhibitory effect on T cell-mediated cytotoxicity Ziani, Linda Buart, Stéphanie Chouaib, Salem Thiery, Jerome Oncoimmunology Original Research Cancer-associated fibroblasts (CAFs) and hypoxia are central players in the complex process of tumor cell-stroma interaction and are involved in the alteration of the anti-tumor immune response by impacting both cancer and immune cell populations. However, even if their independent immunomodulatory properties are now well documented, whether the interaction between these two components of the tumor microenvironment can affect CAFs ability to alter the anti-tumor immune response is still poorly defined. In this study, we provide evidence that hypoxia increases melanoma-associated fibroblasts expression and/or secretion of several immunosuppressive factors (including TGF-β, IL6, IL10, VEGF and PD-L1). Moreover, we demonstrate that hypoxic CAF secretome exerts a more profound effect on T cell-mediated cytotoxicity than its normoxic counterpart. Together, our data suggest that the crosstalk between hypoxia and CAFs is probably an important determinant in the complex immunosuppressive tumor microenvironment. Taylor & Francis 2021-07-25 /pmc/articles/PMC8312612/ /pubmed/34367731 http://dx.doi.org/10.1080/2162402X.2021.1950953 Text en © 2021 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Research Ziani, Linda Buart, Stéphanie Chouaib, Salem Thiery, Jerome Hypoxia increases melanoma-associated fibroblasts immunosuppressive potential and inhibitory effect on T cell-mediated cytotoxicity |
title | Hypoxia increases melanoma-associated fibroblasts immunosuppressive potential and inhibitory effect on T cell-mediated cytotoxicity |
title_full | Hypoxia increases melanoma-associated fibroblasts immunosuppressive potential and inhibitory effect on T cell-mediated cytotoxicity |
title_fullStr | Hypoxia increases melanoma-associated fibroblasts immunosuppressive potential and inhibitory effect on T cell-mediated cytotoxicity |
title_full_unstemmed | Hypoxia increases melanoma-associated fibroblasts immunosuppressive potential and inhibitory effect on T cell-mediated cytotoxicity |
title_short | Hypoxia increases melanoma-associated fibroblasts immunosuppressive potential and inhibitory effect on T cell-mediated cytotoxicity |
title_sort | hypoxia increases melanoma-associated fibroblasts immunosuppressive potential and inhibitory effect on t cell-mediated cytotoxicity |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312612/ https://www.ncbi.nlm.nih.gov/pubmed/34367731 http://dx.doi.org/10.1080/2162402X.2021.1950953 |
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