| First Author | Pires-Afonso Y | Year | 2022 |
| Journal | Mol Oncol | Volume | 16 |
| Issue | 17 | Pages | 3167-3191 |
| PubMed ID | 35838338 | Mgi Jnum | J:333766 |
| Mgi Id | MGI:7440147 | Doi | 10.1002/1878-0261.13287 |
| Citation | Pires-Afonso Y, et al. (2022) Elucidating tumour-associated microglia/macrophage diversity along glioblastoma progression and under ACOD1 deficiency. Mol Oncol 16(17):3167-3191 |
| abstractText | 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. |
