Immunological synapse formation between T regulatory cells and cancer-associated fibroblasts promotes tumour development.

Autor: Varveri, Athina, Papadopoulou, Miranta, Papadovasilakis, Zacharias, Compeer, Ewoud B., Legaki, Aigli-Ioanna, Delis, Anastasios, Damaskou, Vasileia, Boon, Louis, Papadogiorgaki, Sevasti, Samiotaki, Martina, Foukas, Periklis G., Eliopoulos, Aristides G., Hatzioannou, Aikaterini, Alissafi, Themis, Dustin, Michael L., Verginis, Panayotis
Předmět:
Zdroj: Nature Communications; 6/11/2024, Vol. 15 Issue 1, p1-19, 19p
Abstrakt: 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. 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]
Databáze: Complementary Index
Externí odkaz: