دورية أكاديمية

Elucidating tumour‐associated microglia/macrophage diversity along glioblastoma progression and under ACOD1 deficiency

التفاصيل البيبلوغرافية
العنوان: Elucidating tumour‐associated microglia/macrophage diversity along glioblastoma progression and under ACOD1 deficiency
المؤلفون: Yolanda Pires‐Afonso, Arnaud Muller, Kamil Grzyb, Anaïs Oudin, Yahaya A. Yabo, Carole Sousa, Andrea Scafidi, Aurélie Poli, Antonio Cosma, Rashi Halder, Djalil Coowar, Anna Golebiewska, Alexander Skupin, Simone P. Niclou, Alessandro Michelucci
المصدر: Molecular Oncology, Vol 16, Iss 17, Pp 3167-3191 (2022)
بيانات النشر: Wiley, 2022.
سنة النشر: 2022
المجموعة: LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
مصطلحات موضوعية: ACOD1/IRG1, glioblastoma, heterogeneity, metabolic reprogramming, single‐cell RNA‐sequencing, tumour‐associated microglia/macrophages, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
الوصف: 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.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1878-0261
1574-7891
العلاقة: https://doaj.org/toc/1574-7891Test; https://doaj.org/toc/1878-0261Test
DOI: 10.1002/1878-0261.13287
الوصول الحر: https://doaj.org/article/7cce8814107e4c53bb9804c062f2799fTest
رقم الانضمام: edsdoj.7cce8814107e4c53bb9804c062f2799f
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:18780261
15747891
DOI:10.1002/1878-0261.13287