| Autor: |
Athina Varveri, Miranta Papadopoulou, Zacharias Papadovasilakis, Ewoud B. Compeer, Aigli-Ioanna Legaki, Anastasios Delis, Vasileia Damaskou, Louis Boon, Sevasti Papadogiorgaki, Martina Samiotaki, Periklis G. Foukas, Aristides G. Eliopoulos, Aikaterini Hatzioannou, Themis Alissafi, Michael L. Dustin, Panayotis Verginis |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Nature Communications, Vol 15, Iss 1, Pp 1-19 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2041-1723 |
| DOI: |
10.1038/s41467-024-49282-1 |
| Popis: |
Abstract Cancer-associated fibroblasts (CAFs) have emerged as a dominant non-hematopoietic cell population in the tumour microenvironment, serving diverse functions in tumour progression. However, the mechanisms via which CAFs influence the anti-tumour immunity remain poorly understood. Here, using multiple tumour models and biopsies from cancer patients, we report that α-SMA+ CAFs can form immunological synapses with Foxp3+ regulatory T cells (Tregs) in tumours. Notably, α-SMA+ CAFs can phagocytose and process tumour antigens and exhibit a tolerogenic phenotype which instructs movement arrest, activation and proliferation in Tregs in an antigen-specific manner. Moreover, α-SMA+ CAFs display double-membrane structures resembling autophagosomes in their cytoplasm. Single-cell transcriptomic data showed an enrichment in autophagy and antigen processing/presentation pathways in α-SMA-expressing CAF clusters. Conditional knockout of Atg5 in α-SMA+ CAFs promoted inflammatory re-programming in CAFs, reduced Treg cell infiltration and attenuated tumour development. Overall, our findings reveal an immunosuppressive mechanism entailing the formation of synapses between α-SMA+ CAFs and Tregs in an autophagy-dependent manner. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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