Extracellular vesicles released by cancer-associated fibroblast-induced myeloid-derived suppressor cells inhibit T-cell function

Autor: Carlo P. Ramil, Handan Xiang, Peng Zhang, Aileen Cronin, Lisia Cabral, Zhizhang Yin, Josephine Hai, Huijun Wang, Benjamin Ruprecht, Yanlin Jia, Dongyu Sun, Hongmin Chen, An Chi
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: OncoImmunology, Vol 13, Iss 1 (2024)
Druh dokumentu: article
ISSN: 2162402X
2162-402X
DOI: 10.1080/2162402X.2023.2300882
Popis: ABSTRACTMyeloid cells are known to play a crucial role in creating a tumor-promoting and immune suppressive microenvironment. Our previous study demonstrated that primary human monocytes can be polarized into immunosuppressive myeloid-derived suppressor cells (MDSCs) by cancer-associated fibroblasts (CAFs) in a 3D co-culture system. However, the molecular mechanisms underlying the immunosuppressive function of MDSCs, especially CAF-induced MDSCs, remain poorly understood. Using mass spectrometry-based proteomics, we compared cell surface protein changes among monocytes, in vitro differentiated CAF-induced MDSCs, M1/M2 macrophages, and dendritic cells, and identified an extracellular vesicle (EV)-mediated secretory phenotype of MDSCs. Functional assays using an MDSC/T-cell co-culture system revealed that blocking EV generation in CAF-induced MDSCs reversed their ability to suppress T-cell proliferation, while EVs isolated from CAF-induced MDSCs directly inhibited T-cell function. Furthermore, we identified fructose bisphosphatase 1 (FBP1) as a cargo protein that is highly enriched in EVs isolated from CAF-induced MDSCs, and pharmacological inhibition of FBP1 partially reversed the suppressive phenotype of MDSCs. Our findings provide valuable insights into the cell surface proteome of different monocyte-derived myeloid subsets and uncover a novel mechanism underlying the interplay between CAFs and myeloid cells in shaping a tumor-permissive microenvironment.
Databáze: Directory of Open Access Journals
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