Extracellular vesicles released by cancer-associated fibroblast-induced myeloid-derived suppressor cells inhibit T-cell function
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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2023.2300882 |
| _version_ | 1797364550809419776 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Carlo P. Ramil |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T16:37:50Z |
| format | Article |
| id | doaj.art-0a8619fc60474ca5893566aab3adaec4 |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-03-08T16:37:50Z |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-0a8619fc60474ca5893566aab3adaec42024-01-05T12:13:07ZengTaylor & Francis GroupOncoImmunology2162-402X2024-12-0113110.1080/2162402X.2023.2300882Extracellular vesicles released by cancer-associated fibroblast-induced myeloid-derived suppressor cells inhibit T-cell functionCarlo P. Ramil0Handan Xiang1Peng Zhang2Aileen Cronin3Lisia Cabral4Zhizhang Yin5Josephine Hai6Huijun Wang7Benjamin Ruprecht8Yanlin Jia9Dongyu Sun10Hongmin Chen11An Chi12Chemical Biology, Merck & Co. Inc, Cambridge, MA, USADiscovery Immunology, Merck & Co. Inc, Cambridge, MA, USAChemical Biology, Merck & Co. Inc, Cambridge, MA, USAChemical Biology, Merck & Co. Inc, Cambridge, MA, USAChemical Biology, Merck & Co. Inc, Cambridge, MA, USANeuroimmunology, Merck & Co. Inc, Boston, MA, USAQuantitative Biosciences, Merck & Co. Inc, Boston, MA, USAComputational and Structural Chemistry, Merck & Co. Inc, Kenilworth, NJ, USAChemical Biology, Merck & Co. Inc, Cambridge, MA, USADiscovery Immunology, Merck & Co. Inc, Cambridge, MA, USAQuantitative Biosciences, Merck & Co. Inc, Boston, MA, USAQuantitative Biosciences, Merck & Co. Inc, Boston, MA, USAChemical Biology, Merck & Co. Inc, Cambridge, MA, USAABSTRACTMyeloid 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.https://www.tandfonline.com/doi/10.1080/2162402X.2023.2300882Cancer-associated fibroblasts (CAF)extracellular vesicles (EV)myeloid-derived suppressor cells (MDSC)proteomics |
| spellingShingle | 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 Extracellular vesicles released by cancer-associated fibroblast-induced myeloid-derived suppressor cells inhibit T-cell function OncoImmunology Cancer-associated fibroblasts (CAF) extracellular vesicles (EV) myeloid-derived suppressor cells (MDSC) proteomics |
| title | Extracellular vesicles released by cancer-associated fibroblast-induced myeloid-derived suppressor cells inhibit T-cell function |
| title_full | Extracellular vesicles released by cancer-associated fibroblast-induced myeloid-derived suppressor cells inhibit T-cell function |
| title_fullStr | Extracellular vesicles released by cancer-associated fibroblast-induced myeloid-derived suppressor cells inhibit T-cell function |
| title_full_unstemmed | Extracellular vesicles released by cancer-associated fibroblast-induced myeloid-derived suppressor cells inhibit T-cell function |
| title_short | Extracellular vesicles released by cancer-associated fibroblast-induced myeloid-derived suppressor cells inhibit T-cell function |
| title_sort | extracellular vesicles released by cancer associated fibroblast induced myeloid derived suppressor cells inhibit t cell function |
| topic | Cancer-associated fibroblasts (CAF) extracellular vesicles (EV) myeloid-derived suppressor cells (MDSC) proteomics |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2023.2300882 |
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