Exploiting Manipulated Small Extracellular Vesicles to Subvert Immunosuppression at the Tumor Microenvironment through Mannose Receptor/CD206 Targeting
Immunosuppression at tumor microenvironment (TME) is one of the major obstacles to be overcome for an effective therapeutic intervention against solid tumors. Tumor-associated macrophages (TAMs) comprise a sub-population that plays multiple pro-tumoral roles in tumor development including general im...
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| Format: | Article |
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MDPI AG
2020-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/17/6318 |
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| author | Maria Luisa Fiani Valeria Barreca Massimo Sargiacomo Flavia Ferrantelli Francesco Manfredi Maurizio Federico |
| author_facet | Maria Luisa Fiani Valeria Barreca Massimo Sargiacomo Flavia Ferrantelli Francesco Manfredi Maurizio Federico |
| author_sort | Maria Luisa Fiani |
| collection | DOAJ |
| description | Immunosuppression at tumor microenvironment (TME) is one of the major obstacles to be overcome for an effective therapeutic intervention against solid tumors. Tumor-associated macrophages (TAMs) comprise a sub-population that plays multiple pro-tumoral roles in tumor development including general immunosuppression, which can be identified in terms of high expression of mannose receptor (MR or CD206). Immunosuppressive TAMs, like other macrophage sub-populations, display functional plasticity that allows them to be re-programmed to inflammatory macrophages. In order to mitigate immunosuppression at the TME, several efforts are ongoing to effectively re-educate pro-tumoral TAMs. Extracellular vesicles (EVs), released by both normal and tumor cells types, are emerging as key mediators of the cell to cell communication and have been shown to have a role in the modulation of immune responses in the TME. Recent studies demonstrated the enrichment of high mannose glycans on the surface of small EVs (sEVs), a subtype of EVs of endosomal origin of 30–150 nm in diameter. This characteristic renders sEVs an ideal tool for the delivery of therapeutic molecules into MR/CD206-expressing TAMs. In this review, we report the most recent literature data highlighting the critical role of TAMs in tumor development, as well as the experimental evidences that has emerged from the biochemical characterization of sEV membranes. In addition, we propose an original way to target immunosuppressive TAMs at the TME by endogenously engineered sEVs for a new therapeutic approach against solid tumors. |
| first_indexed | 2024-03-10T16:40:35Z |
| format | Article |
| id | doaj.art-32dae631104a4534960f050e45be3924 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T16:40:35Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-32dae631104a4534960f050e45be39242023-11-20T12:03:27ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-08-012117631810.3390/ijms21176318Exploiting Manipulated Small Extracellular Vesicles to Subvert Immunosuppression at the Tumor Microenvironment through Mannose Receptor/CD206 TargetingMaria Luisa Fiani0Valeria Barreca1Massimo Sargiacomo2Flavia Ferrantelli3Francesco Manfredi4Maurizio Federico5National Center for Global Health, Istituto Superiore di Sanità, 00161 Rome, ItalyNational Center for Global Health, Istituto Superiore di Sanità, 00161 Rome, ItalyNational Center for Global Health, Istituto Superiore di Sanità, 00161 Rome, ItalyNational Center for Global Health, Istituto Superiore di Sanità, 00161 Rome, ItalyNational Center for Global Health, Istituto Superiore di Sanità, 00161 Rome, ItalyNational Center for Global Health, Istituto Superiore di Sanità, 00161 Rome, ItalyImmunosuppression at tumor microenvironment (TME) is one of the major obstacles to be overcome for an effective therapeutic intervention against solid tumors. Tumor-associated macrophages (TAMs) comprise a sub-population that plays multiple pro-tumoral roles in tumor development including general immunosuppression, which can be identified in terms of high expression of mannose receptor (MR or CD206). Immunosuppressive TAMs, like other macrophage sub-populations, display functional plasticity that allows them to be re-programmed to inflammatory macrophages. In order to mitigate immunosuppression at the TME, several efforts are ongoing to effectively re-educate pro-tumoral TAMs. Extracellular vesicles (EVs), released by both normal and tumor cells types, are emerging as key mediators of the cell to cell communication and have been shown to have a role in the modulation of immune responses in the TME. Recent studies demonstrated the enrichment of high mannose glycans on the surface of small EVs (sEVs), a subtype of EVs of endosomal origin of 30–150 nm in diameter. This characteristic renders sEVs an ideal tool for the delivery of therapeutic molecules into MR/CD206-expressing TAMs. In this review, we report the most recent literature data highlighting the critical role of TAMs in tumor development, as well as the experimental evidences that has emerged from the biochemical characterization of sEV membranes. In addition, we propose an original way to target immunosuppressive TAMs at the TME by endogenously engineered sEVs for a new therapeutic approach against solid tumors.https://www.mdpi.com/1422-0067/21/17/6318tumor-associated macrophagestumor microenvironmentmacrophage polarizationmannose receptorexosomesextracellular vesicles |
| spellingShingle | Maria Luisa Fiani Valeria Barreca Massimo Sargiacomo Flavia Ferrantelli Francesco Manfredi Maurizio Federico Exploiting Manipulated Small Extracellular Vesicles to Subvert Immunosuppression at the Tumor Microenvironment through Mannose Receptor/CD206 Targeting International Journal of Molecular Sciences tumor-associated macrophages tumor microenvironment macrophage polarization mannose receptor exosomes extracellular vesicles |
| title | Exploiting Manipulated Small Extracellular Vesicles to Subvert Immunosuppression at the Tumor Microenvironment through Mannose Receptor/CD206 Targeting |
| title_full | Exploiting Manipulated Small Extracellular Vesicles to Subvert Immunosuppression at the Tumor Microenvironment through Mannose Receptor/CD206 Targeting |
| title_fullStr | Exploiting Manipulated Small Extracellular Vesicles to Subvert Immunosuppression at the Tumor Microenvironment through Mannose Receptor/CD206 Targeting |
| title_full_unstemmed | Exploiting Manipulated Small Extracellular Vesicles to Subvert Immunosuppression at the Tumor Microenvironment through Mannose Receptor/CD206 Targeting |
| title_short | Exploiting Manipulated Small Extracellular Vesicles to Subvert Immunosuppression at the Tumor Microenvironment through Mannose Receptor/CD206 Targeting |
| title_sort | exploiting manipulated small extracellular vesicles to subvert immunosuppression at the tumor microenvironment through mannose receptor cd206 targeting |
| topic | tumor-associated macrophages tumor microenvironment macrophage polarization mannose receptor exosomes extracellular vesicles |
| url | https://www.mdpi.com/1422-0067/21/17/6318 |
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