Renal cancer-derived exosomes induce tumor immune tolerance by MDSCs-mediated antigen-specific immunosuppression
Abstract Backgound Although Myeloid-derived suppressor cells (MDSCs) have a prominent ability to suppress the immune responses of T lymphocytes and propel tumor immune escape, a lack of profound systemic immunesuppression in tumor-bearing mice and tumor patients. The underlying mechanism of these re...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-07-01
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| Series: | Cell Communication and Signaling |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12964-020-00611-z |
| _version_ | 1830475470533033984 |
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| author | Yingying Gao Haoyu Xu Nan Li Hexi Wang Lei Ma Shiyou Chen Jiayu Liu Yongbo Zheng Yao Zhang |
| author_facet | Yingying Gao Haoyu Xu Nan Li Hexi Wang Lei Ma Shiyou Chen Jiayu Liu Yongbo Zheng Yao Zhang |
| author_sort | Yingying Gao |
| collection | DOAJ |
| description | Abstract Backgound Although Myeloid-derived suppressor cells (MDSCs) have a prominent ability to suppress the immune responses of T lymphocytes and propel tumor immune escape, a lack of profound systemic immunesuppression in tumor-bearing mice and tumor patients. The underlying mechanism of these remains unclear. Methods For this purpose, renal cancer-derived exosomes (RDEs) were first labeled with PKH67 and been observed the internalization by MDSCs. Flow cytometry analysis showed the proportion and activity change of MDSCs in spleen and bone marrow induced by RDEs. Further, western blot experiments were used to verify triggered mechanism of MDSCs by RDEs. Finally, proliferation and cytotoxicity of cytotoxic T lymphocytes (CTLs) co-cultured with MDSCs in vitro and a series of experiments in vivo were performed to demonstrate the specific inhibitory effect of RDEs-induced MDSCs. Results This study suggested that RDEs crucially contributed to presenting antigenic information, activating and driving specific immunosuppressive effect to MDSCs. HSP70, which is highly expressed in RDEs, initiate this process in a toll like receptor 2 (TLR2)-dependent manner. Importantly, RDEs-induced MDSCs could exert an antigen-specific immunosuppression effect on CTL and specific promote renal tumors-growth and immune escape in consequence. Conclusion The immunosuppression mediated by MDSCs which is induced by RDEs is antigen-specific. HSP70, which is highly expressed in RDEs, plays a pivotal role in this process. Targeted abrogating the function of MDSCs, or eliminating the expression of HSP70 in exosomes, or blocking the crosstalk between them provides a new direction and theoretical support for future immunotherapy. Video abstract Graphical abstract |
| first_indexed | 2024-12-21T15:36:56Z |
| format | Article |
| id | doaj.art-d195df14fa8a4991ba46f4549ffabedc |
| institution | Directory Open Access Journal |
| issn | 1478-811X |
| language | English |
| last_indexed | 2024-12-21T15:36:56Z |
| publishDate | 2020-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj.art-d195df14fa8a4991ba46f4549ffabedc2022-12-21T18:58:37ZengBMCCell Communication and Signaling1478-811X2020-07-0118111410.1186/s12964-020-00611-zRenal cancer-derived exosomes induce tumor immune tolerance by MDSCs-mediated antigen-specific immunosuppressionYingying Gao0Haoyu Xu1Nan Li2Hexi Wang3Lei Ma4Shiyou Chen5Jiayu Liu6Yongbo Zheng7Yao Zhang8Department of Laboratory Diagnosis, Chongqing Medical UniversityDepartment of Urology, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Urology, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Urology, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Laboratory Diagnosis, The First Affiliated Hospital of Jiamusi UniversityDepartment of Urology, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Urology, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Urology, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Urology, The First Affiliated Hospital of Chongqing Medical UniversityAbstract Backgound Although Myeloid-derived suppressor cells (MDSCs) have a prominent ability to suppress the immune responses of T lymphocytes and propel tumor immune escape, a lack of profound systemic immunesuppression in tumor-bearing mice and tumor patients. The underlying mechanism of these remains unclear. Methods For this purpose, renal cancer-derived exosomes (RDEs) were first labeled with PKH67 and been observed the internalization by MDSCs. Flow cytometry analysis showed the proportion and activity change of MDSCs in spleen and bone marrow induced by RDEs. Further, western blot experiments were used to verify triggered mechanism of MDSCs by RDEs. Finally, proliferation and cytotoxicity of cytotoxic T lymphocytes (CTLs) co-cultured with MDSCs in vitro and a series of experiments in vivo were performed to demonstrate the specific inhibitory effect of RDEs-induced MDSCs. Results This study suggested that RDEs crucially contributed to presenting antigenic information, activating and driving specific immunosuppressive effect to MDSCs. HSP70, which is highly expressed in RDEs, initiate this process in a toll like receptor 2 (TLR2)-dependent manner. Importantly, RDEs-induced MDSCs could exert an antigen-specific immunosuppression effect on CTL and specific promote renal tumors-growth and immune escape in consequence. Conclusion The immunosuppression mediated by MDSCs which is induced by RDEs is antigen-specific. HSP70, which is highly expressed in RDEs, plays a pivotal role in this process. Targeted abrogating the function of MDSCs, or eliminating the expression of HSP70 in exosomes, or blocking the crosstalk between them provides a new direction and theoretical support for future immunotherapy. Video abstract Graphical abstracthttp://link.springer.com/article/10.1186/s12964-020-00611-zRDEsMDSCsAntigen-specificityTumor immune escapeHSP70 |
| spellingShingle | Yingying Gao Haoyu Xu Nan Li Hexi Wang Lei Ma Shiyou Chen Jiayu Liu Yongbo Zheng Yao Zhang Renal cancer-derived exosomes induce tumor immune tolerance by MDSCs-mediated antigen-specific immunosuppression Cell Communication and Signaling RDEs MDSCs Antigen-specificity Tumor immune escape HSP70 |
| title | Renal cancer-derived exosomes induce tumor immune tolerance by MDSCs-mediated antigen-specific immunosuppression |
| title_full | Renal cancer-derived exosomes induce tumor immune tolerance by MDSCs-mediated antigen-specific immunosuppression |
| title_fullStr | Renal cancer-derived exosomes induce tumor immune tolerance by MDSCs-mediated antigen-specific immunosuppression |
| title_full_unstemmed | Renal cancer-derived exosomes induce tumor immune tolerance by MDSCs-mediated antigen-specific immunosuppression |
| title_short | Renal cancer-derived exosomes induce tumor immune tolerance by MDSCs-mediated antigen-specific immunosuppression |
| title_sort | renal cancer derived exosomes induce tumor immune tolerance by mdscs mediated antigen specific immunosuppression |
| topic | RDEs MDSCs Antigen-specificity Tumor immune escape HSP70 |
| url | http://link.springer.com/article/10.1186/s12964-020-00611-z |
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