Extracellular Vesicles From Gastric Cancer Cells Induce PD-L1 Expression on Neutrophils to Suppress T-Cell Immunity
Neutrophils are prominent components of solid tumors and exhibit distinct phenotypes in different tumor milieu. We have previously shown that tumor extracellular vesicles (EVs) could induce pro-tumor activation of neutrophils; however, the role of tumor EV-elicited neutrophils in tumor immunity rema...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-05-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2020.00629/full |
| _version_ | 1819111643887435776 |
|---|---|
| author | Yinghong Shi Yinghong Shi Jiahui Zhang Jiahui Zhang Zheying Mao Zheying Mao Han Jiang Han Jiang Wei Liu Wei Liu Hui Shi Hui Shi Runbi Ji Runbi Ji Wenrong Xu Wenrong Xu Hui Qian Hui Qian Xu Zhang Xu Zhang |
| author_facet | Yinghong Shi Yinghong Shi Jiahui Zhang Jiahui Zhang Zheying Mao Zheying Mao Han Jiang Han Jiang Wei Liu Wei Liu Hui Shi Hui Shi Runbi Ji Runbi Ji Wenrong Xu Wenrong Xu Hui Qian Hui Qian Xu Zhang Xu Zhang |
| author_sort | Yinghong Shi |
| collection | DOAJ |
| description | Neutrophils are prominent components of solid tumors and exhibit distinct phenotypes in different tumor milieu. We have previously shown that tumor extracellular vesicles (EVs) could induce pro-tumor activation of neutrophils; however, the role of tumor EV-elicited neutrophils in tumor immunity remains unclear. Herein, we reported that gastric cancer cell-derived EVs (GC-EVs) induced the expression of programmed death-ligand 1 (PD-L1) on neutrophils. GC-EVs transported high-mobility group box-1 (HMGB1) to activate signal transducer and activator of transcription 3 (STAT3) and upregulate PD-L1 gene expression in neutrophils. Blocking STAT3 pathway and silencing HMGB1 reversed GC-EV-induced PD-L1 expression on neutrophils. GC-EV-elicited neutrophils suppressed T cell proliferation, activation, and function in vitro, which could be antagonized by a specific PD-L1 antibody. Furthermore, GC tissue-derived EVs also showed similar effects. Taken together, our results indicate that EVs from the GC microenvironment induce PD-L1 expression on neutrophils to suppress T-cell immunity, which provides a new insight into the pro-tumor roles of neutrophils in GC and sheds light on the multifaceted roles of EVs in orchestrating an immunosuppressive microenvironment. |
| first_indexed | 2024-12-22T04:00:53Z |
| format | Article |
| id | doaj.art-3f410703a63d43e2b7533088e6894844 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-22T04:00:53Z |
| publishDate | 2020-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-3f410703a63d43e2b7533088e68948442022-12-21T18:39:44ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-05-011010.3389/fonc.2020.00629531984Extracellular Vesicles From Gastric Cancer Cells Induce PD-L1 Expression on Neutrophils to Suppress T-Cell ImmunityYinghong Shi0Yinghong Shi1Jiahui Zhang2Jiahui Zhang3Zheying Mao4Zheying Mao5Han Jiang6Han Jiang7Wei Liu8Wei Liu9Hui Shi10Hui Shi11Runbi Ji12Runbi Ji13Wenrong Xu14Wenrong Xu15Hui Qian16Hui Qian17Xu Zhang18Xu Zhang19Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, ChinaZhenjiang Key Laboratory of High Technology for Basic and Translational Research on Exosomes, Zhenjiang, ChinaJiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, ChinaZhenjiang Key Laboratory of High Technology for Basic and Translational Research on Exosomes, Zhenjiang, ChinaJiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, ChinaZhenjiang Key Laboratory of High Technology for Basic and Translational Research on Exosomes, Zhenjiang, ChinaJiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, ChinaZhenjiang Key Laboratory of High Technology for Basic and Translational Research on Exosomes, Zhenjiang, ChinaJiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, ChinaZhenjiang Key Laboratory of High Technology for Basic and Translational Research on Exosomes, Zhenjiang, ChinaJiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, ChinaZhenjiang Key Laboratory of High Technology for Basic and Translational Research on Exosomes, Zhenjiang, ChinaZhenjiang Key Laboratory of High Technology for Basic and Translational Research on Exosomes, Zhenjiang, ChinaDepartment of Clinical Laboratory, The Affiliated People's Hospital of Jiangsu University, Zhenjiang, ChinaJiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, ChinaZhenjiang Key Laboratory of High Technology for Basic and Translational Research on Exosomes, Zhenjiang, ChinaJiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, ChinaZhenjiang Key Laboratory of High Technology for Basic and Translational Research on Exosomes, Zhenjiang, ChinaJiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, ChinaZhenjiang Key Laboratory of High Technology for Basic and Translational Research on Exosomes, Zhenjiang, ChinaNeutrophils are prominent components of solid tumors and exhibit distinct phenotypes in different tumor milieu. We have previously shown that tumor extracellular vesicles (EVs) could induce pro-tumor activation of neutrophils; however, the role of tumor EV-elicited neutrophils in tumor immunity remains unclear. Herein, we reported that gastric cancer cell-derived EVs (GC-EVs) induced the expression of programmed death-ligand 1 (PD-L1) on neutrophils. GC-EVs transported high-mobility group box-1 (HMGB1) to activate signal transducer and activator of transcription 3 (STAT3) and upregulate PD-L1 gene expression in neutrophils. Blocking STAT3 pathway and silencing HMGB1 reversed GC-EV-induced PD-L1 expression on neutrophils. GC-EV-elicited neutrophils suppressed T cell proliferation, activation, and function in vitro, which could be antagonized by a specific PD-L1 antibody. Furthermore, GC tissue-derived EVs also showed similar effects. Taken together, our results indicate that EVs from the GC microenvironment induce PD-L1 expression on neutrophils to suppress T-cell immunity, which provides a new insight into the pro-tumor roles of neutrophils in GC and sheds light on the multifaceted roles of EVs in orchestrating an immunosuppressive microenvironment.https://www.frontiersin.org/article/10.3389/fonc.2020.00629/fullextracellular vesiclesprogrammed death-ligand 1 (PD-L1)neutrophilsimmune suppressiongastric cancer |
| spellingShingle | Yinghong Shi Yinghong Shi Jiahui Zhang Jiahui Zhang Zheying Mao Zheying Mao Han Jiang Han Jiang Wei Liu Wei Liu Hui Shi Hui Shi Runbi Ji Runbi Ji Wenrong Xu Wenrong Xu Hui Qian Hui Qian Xu Zhang Xu Zhang Extracellular Vesicles From Gastric Cancer Cells Induce PD-L1 Expression on Neutrophils to Suppress T-Cell Immunity Frontiers in Oncology extracellular vesicles programmed death-ligand 1 (PD-L1) neutrophils immune suppression gastric cancer |
| title | Extracellular Vesicles From Gastric Cancer Cells Induce PD-L1 Expression on Neutrophils to Suppress T-Cell Immunity |
| title_full | Extracellular Vesicles From Gastric Cancer Cells Induce PD-L1 Expression on Neutrophils to Suppress T-Cell Immunity |
| title_fullStr | Extracellular Vesicles From Gastric Cancer Cells Induce PD-L1 Expression on Neutrophils to Suppress T-Cell Immunity |
| title_full_unstemmed | Extracellular Vesicles From Gastric Cancer Cells Induce PD-L1 Expression on Neutrophils to Suppress T-Cell Immunity |
| title_short | Extracellular Vesicles From Gastric Cancer Cells Induce PD-L1 Expression on Neutrophils to Suppress T-Cell Immunity |
| title_sort | extracellular vesicles from gastric cancer cells induce pd l1 expression on neutrophils to suppress t cell immunity |
| topic | extracellular vesicles programmed death-ligand 1 (PD-L1) neutrophils immune suppression gastric cancer |
| url | https://www.frontiersin.org/article/10.3389/fonc.2020.00629/full |
| work_keys_str_mv | AT yinghongshi extracellularvesiclesfromgastriccancercellsinducepdl1expressiononneutrophilstosuppresstcellimmunity AT yinghongshi extracellularvesiclesfromgastriccancercellsinducepdl1expressiononneutrophilstosuppresstcellimmunity AT jiahuizhang extracellularvesiclesfromgastriccancercellsinducepdl1expressiononneutrophilstosuppresstcellimmunity AT jiahuizhang extracellularvesiclesfromgastriccancercellsinducepdl1expressiononneutrophilstosuppresstcellimmunity AT zheyingmao extracellularvesiclesfromgastriccancercellsinducepdl1expressiononneutrophilstosuppresstcellimmunity AT zheyingmao extracellularvesiclesfromgastriccancercellsinducepdl1expressiononneutrophilstosuppresstcellimmunity AT hanjiang extracellularvesiclesfromgastriccancercellsinducepdl1expressiononneutrophilstosuppresstcellimmunity AT hanjiang extracellularvesiclesfromgastriccancercellsinducepdl1expressiononneutrophilstosuppresstcellimmunity AT weiliu extracellularvesiclesfromgastriccancercellsinducepdl1expressiononneutrophilstosuppresstcellimmunity AT weiliu extracellularvesiclesfromgastriccancercellsinducepdl1expressiononneutrophilstosuppresstcellimmunity AT huishi extracellularvesiclesfromgastriccancercellsinducepdl1expressiononneutrophilstosuppresstcellimmunity AT huishi extracellularvesiclesfromgastriccancercellsinducepdl1expressiononneutrophilstosuppresstcellimmunity AT runbiji extracellularvesiclesfromgastriccancercellsinducepdl1expressiononneutrophilstosuppresstcellimmunity AT runbiji extracellularvesiclesfromgastriccancercellsinducepdl1expressiononneutrophilstosuppresstcellimmunity AT wenrongxu extracellularvesiclesfromgastriccancercellsinducepdl1expressiononneutrophilstosuppresstcellimmunity AT wenrongxu extracellularvesiclesfromgastriccancercellsinducepdl1expressiononneutrophilstosuppresstcellimmunity AT huiqian extracellularvesiclesfromgastriccancercellsinducepdl1expressiononneutrophilstosuppresstcellimmunity AT huiqian extracellularvesiclesfromgastriccancercellsinducepdl1expressiononneutrophilstosuppresstcellimmunity AT xuzhang extracellularvesiclesfromgastriccancercellsinducepdl1expressiononneutrophilstosuppresstcellimmunity AT xuzhang extracellularvesiclesfromgastriccancercellsinducepdl1expressiononneutrophilstosuppresstcellimmunity |