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Immunological synapse formation between T regulatory cells and cancer-associated fibroblasts promotes tumour development.
- Source :
- Nature Communications; 6/11/2024, Vol. 15 Issue 1, p1-19, 19p
- Publication Year :
- 2024
-
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<superscript>+</superscript> CAFs can form immunological synapses with Foxp3<superscript>+</superscript> regulatory T cells (Tregs) in tumours. Notably, α-SMA<superscript>+</superscript> 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<superscript>+</superscript> 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<superscript>+</superscript> 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<superscript>+</superscript> CAFs and Tregs in an autophagy-dependent manner. Cancer-associated fibroblasts (CAFs) are a predominant stromal cell population in the tumour microenvironment. Here, the authors demonstrate that αSMA + CAFs can form an immunological synapse with regulatory T cells (Tregs) in tumours, which results in Treg activation and expansion in a process that is antigen- and autophagy-dependent. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 15
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Nature Communications
- Publication Type :
- Academic Journal
- Accession number :
- 177817247
- Full Text :
- https://doi.org/10.1038/s41467-024-49282-1