Cancer-associated Fibroblast-derived Extracellular Vesicles Mediate Immune Escape of Bladder Cancer via PD-L1/PD-1 Expression.

Autor:	Feng R; Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, P.R. China.; Department of Urology, Zhenjiang Hospital of Chinese Traditional and Western Medicine, Zhenjiang, 212002, Jiangsu, P.R. China., Li Z; Department of Urology, Zhenjiang Hospital of Chinese Traditional and Western Medicine, Zhenjiang, 212002, Jiangsu, P.R. China., Ge G; Department of Urology, Zhenjiang Hospital of Chinese Traditional and Western Medicine, Zhenjiang, 212002, Jiangsu, P.R. China., Wang C; Department of Urology, Zhenjiang Hospital of Chinese Traditional and Western Medicine, Zhenjiang, 212002, Jiangsu, P.R. China., Jia Y; Department of Urology, Zhenjiang Hospital of Chinese Traditional and Western Medicine, Zhenjiang, 212002, Jiangsu, P.R. China., Ouyang J; Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, P.R. China.
Jazyk:	angličtina
Zdroj:	Endocrine, metabolic & immune disorders drug targets [Endocr Metab Immune Disord Drug Targets] 2023; Vol. 23 (11), pp. 1410-1420.
DOI:	10.2174/1871530323666230228124125
Abstrakt:	Objective: Bladder cancer (BCa) is a malignant urological tumor with a high prevalence and poor prognosis. Extracellular vesicles (EVs) are increasingly becoming current hotspots owing to their involvement in cancer progression. This paper probed into the action of cancer-associated fibroblast-derived EVs (CAF-EVs) in the immune escape of BCa. Methods: CAFs were identified by immunofluorescence. EVs were extracted from CAFs via ultracentrifugation and later characterized. BCa cells (T24 cell line) were co-cultured with CD8+ T cells and then treated with CAF-EVs. The uptake of EVs by T24 cells was examined by confocal laser microscopy. T24 cell apoptosis and invasion were assessed using flow cytometry and invasion assay. CD8+ T cell proliferation was evaluated using CFSE staining. The levels of cytokines (IFN-γ, IL-2, and TNF-α) were measured by ELISA. PD-L1 and PD-1 levels were determined utilizing RT-qPCR and flow cytometry. BCa mouse models were established to identify the effect of CAF-EVs on BCa progression in vivo. Results: CAF-EVs decreased apoptosis and enhanced invasion of T24 cells, reduced proliferation of CD8+ T cells, and diminished levels of IFN-γ, IL-2, and TNF-α secreted by CD8+ T cells. CAF-EVs promoted the immune escape of T24 cells by carrying PD-L1. Downregulation of PDL1 expression in T24 cells or EVs partially counteracted the promotion of CAF-EVs on immune escape by reducing the binding of PD-L1 and PD-1. Additionally, CAF-EVs raised tumor volume and weight, upregulated PD-L1 expression, and weakened CD8+ T cell infiltration in BCa mice. Conclusion: CAF-EVs facilitate the immune escape of BCa by upregulating PD-L1/PD-1. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
Databáze:	MEDLINE
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