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Elucidating tumour‐associated microglia/macrophage diversity along glioblastoma progression and under ACOD1 deficiency
In glioblastoma (GBM), tumour‐associated microglia/macrophages (TAMs) represent the major cell type of the stromal compartment and contribute to tumour immune escape mechanisms. Thus, targeting TAMs is emerging as a promising strategy for immunotherapy. However, TAM heterogeneity and metabolic adapt...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9441003/ https://www.ncbi.nlm.nih.gov/pubmed/35838338 http://dx.doi.org/10.1002/1878-0261.13287 |
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author | Pires‐Afonso, Yolanda Muller, Arnaud Grzyb, Kamil Oudin, Anaïs Yabo, Yahaya A. Sousa, Carole Scafidi, Andrea Poli, Aurélie Cosma, Antonio Halder, Rashi Coowar, Djalil Golebiewska, Anna Skupin, Alexander Niclou, Simone P. Michelucci, Alessandro |
author_facet | Pires‐Afonso, Yolanda Muller, Arnaud Grzyb, Kamil Oudin, Anaïs Yabo, Yahaya A. Sousa, Carole Scafidi, Andrea Poli, Aurélie Cosma, Antonio Halder, Rashi Coowar, Djalil Golebiewska, Anna Skupin, Alexander Niclou, Simone P. Michelucci, Alessandro |
author_sort | Pires‐Afonso, Yolanda |
collection | PubMed |
description | In glioblastoma (GBM), tumour‐associated microglia/macrophages (TAMs) represent the major cell type of the stromal compartment and contribute to tumour immune escape mechanisms. Thus, targeting TAMs is emerging as a promising strategy for immunotherapy. However, TAM heterogeneity and metabolic adaptation along GBM progression represent critical features for the design of effective TAM‐targeted therapies. Here, we comprehensively study the cellular and molecular changes of TAMs in the GL261 GBM mouse model, combining single‐cell RNA‐sequencing with flow cytometry and immunohistological analyses along GBM progression and in the absence of Acod1 (also known as Irg1), a key gene involved in the metabolic reprogramming of macrophages towards an anti‐inflammatory phenotype. Similarly to patients, we identify distinct TAM profiles, mainly based on their ontogeny, that reiterate the idea that microglia‐ and macrophage‐like cells show key transcriptional differences and dynamically adapt along GBM stages. Notably, we uncover decreased antigen‐presenting cell features and immune reactivity in TAMs along tumour progression that are instead enhanced in Acod1‐deficient mice. Overall, our results provide insight into TAM heterogeneity and highlight a novel role for Acod1 in TAM adaptation during GBM progression. |
format | Online Article Text |
id | pubmed-9441003 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-94410032022-09-09 Elucidating tumour‐associated microglia/macrophage diversity along glioblastoma progression and under ACOD1 deficiency Pires‐Afonso, Yolanda Muller, Arnaud Grzyb, Kamil Oudin, Anaïs Yabo, Yahaya A. Sousa, Carole Scafidi, Andrea Poli, Aurélie Cosma, Antonio Halder, Rashi Coowar, Djalil Golebiewska, Anna Skupin, Alexander Niclou, Simone P. Michelucci, Alessandro Mol Oncol Research Articles In glioblastoma (GBM), tumour‐associated microglia/macrophages (TAMs) represent the major cell type of the stromal compartment and contribute to tumour immune escape mechanisms. Thus, targeting TAMs is emerging as a promising strategy for immunotherapy. However, TAM heterogeneity and metabolic adaptation along GBM progression represent critical features for the design of effective TAM‐targeted therapies. Here, we comprehensively study the cellular and molecular changes of TAMs in the GL261 GBM mouse model, combining single‐cell RNA‐sequencing with flow cytometry and immunohistological analyses along GBM progression and in the absence of Acod1 (also known as Irg1), a key gene involved in the metabolic reprogramming of macrophages towards an anti‐inflammatory phenotype. Similarly to patients, we identify distinct TAM profiles, mainly based on their ontogeny, that reiterate the idea that microglia‐ and macrophage‐like cells show key transcriptional differences and dynamically adapt along GBM stages. Notably, we uncover decreased antigen‐presenting cell features and immune reactivity in TAMs along tumour progression that are instead enhanced in Acod1‐deficient mice. Overall, our results provide insight into TAM heterogeneity and highlight a novel role for Acod1 in TAM adaptation during GBM progression. John Wiley and Sons Inc. 2022-08-15 2022-09 /pmc/articles/PMC9441003/ /pubmed/35838338 http://dx.doi.org/10.1002/1878-0261.13287 Text en © 2022 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Pires‐Afonso, Yolanda Muller, Arnaud Grzyb, Kamil Oudin, Anaïs Yabo, Yahaya A. Sousa, Carole Scafidi, Andrea Poli, Aurélie Cosma, Antonio Halder, Rashi Coowar, Djalil Golebiewska, Anna Skupin, Alexander Niclou, Simone P. Michelucci, Alessandro Elucidating tumour‐associated microglia/macrophage diversity along glioblastoma progression and under ACOD1 deficiency |
title | Elucidating tumour‐associated microglia/macrophage diversity along glioblastoma progression and under
ACOD1
deficiency |
title_full | Elucidating tumour‐associated microglia/macrophage diversity along glioblastoma progression and under
ACOD1
deficiency |
title_fullStr | Elucidating tumour‐associated microglia/macrophage diversity along glioblastoma progression and under
ACOD1
deficiency |
title_full_unstemmed | Elucidating tumour‐associated microglia/macrophage diversity along glioblastoma progression and under
ACOD1
deficiency |
title_short | Elucidating tumour‐associated microglia/macrophage diversity along glioblastoma progression and under
ACOD1
deficiency |
title_sort | elucidating tumour‐associated microglia/macrophage diversity along glioblastoma progression and under
acod1
deficiency |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9441003/ https://www.ncbi.nlm.nih.gov/pubmed/35838338 http://dx.doi.org/10.1002/1878-0261.13287 |
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