Inhibitory effect of myeloid-derived suppressor cells activated by Renca cell-derived exosomes on mouse cytotoxic T lymphocytes in vitro

Objective To investigate the inhibitory effect of myeloid-derived suppressor cells (MDSCs) activated by exosomes derived from Renca cells on the proliferation and killing activity of renal cancer antigen-specific cytotoxic T lymphocytes (CTLs) in vitro. Methods Exosomes derived from Renca cells were...

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Main Authors: XU Haoyu, WANG Hexi, LI Nan, ZHANG Yao
Format: Article
Language:zho
Published: Editorial Office of Journal of Third Military Medical University 2019-05-01
Series:Di-san junyi daxue xuebao
Subjects:
Online Access:http://aammt.tmmu.edu.cn/Upload/rhtml/201811195.htm
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author XU Haoyu
WANG Hexi
LI Nan
ZHANG Yao
author_facet XU Haoyu
WANG Hexi
LI Nan
ZHANG Yao
author_sort XU Haoyu
collection DOAJ
description Objective To investigate the inhibitory effect of myeloid-derived suppressor cells (MDSCs) activated by exosomes derived from Renca cells on the proliferation and killing activity of renal cancer antigen-specific cytotoxic T lymphocytes (CTLs) in vitro. Methods Exosomes derived from Renca cells were purified by ultracentrifugation, and exosome-induced activation of MDSCs was detected using flow cytometry. Mouse dendritic cells (DCs) and CD8+ T cells were isolated to prepare DC-activated renal cancer antigen-specific CTLs. Magnetic beads were used to sort out MDSCs activated by the exosomes, and fluorescence staining with carboxyfluorescein diacetate succinimidyl ester (CFSE) and flow cytometry were performed to assess the inhibitory effect of activated MDSCs on the proliferation of CTLs. MDSCs, CTLs and Renca cells were co-cultured in vitro, and the inhibitory effect of exosomes-activated MDSCs on the killing activity of CTLs was observed using LDH release assay. Results Renca cell-derived exosomes effectively induced the aggregation of MDSCs. We successfully isolated DCs from the mice and obtained DC-activated renal cancer antigen-specific CTLs. Compared with the CTLs cultured alone or in the presence of unactivated MDSCs, the CTLs co-cultured with exosomes-activated MDSCs showed a significantly lower proliferation index and a lower killing rate against Renca cells (P < 0.05). Conclusion MDSCs activated by Renca cell-derived exosomes can inhibit the proliferation and lower the cell-killing efficiency of renal cancer antigen-specific CTLs in vitro, suggesting a significant role of MDSCs in immune escape of renal cancer.
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spelling doaj.art-cf77611fdf9d4f188586ba0f780f22072022-12-21T18:44:03ZzhoEditorial Office of Journal of Third Military Medical UniversityDi-san junyi daxue xuebao1000-54042019-05-01411092393010.16016/j.1000-5404.201811195Inhibitory effect of myeloid-derived suppressor cells activated by Renca cell-derived exosomes on mouse cytotoxic T lymphocytes in vitroXU Haoyu0WANG Hexi1LI Nan2ZHANG Yao3Department of Urology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, ChinaDepartment of Urology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, ChinaDepartment of Urology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, ChinaDepartment of Urology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, ChinaObjective To investigate the inhibitory effect of myeloid-derived suppressor cells (MDSCs) activated by exosomes derived from Renca cells on the proliferation and killing activity of renal cancer antigen-specific cytotoxic T lymphocytes (CTLs) in vitro. Methods Exosomes derived from Renca cells were purified by ultracentrifugation, and exosome-induced activation of MDSCs was detected using flow cytometry. Mouse dendritic cells (DCs) and CD8+ T cells were isolated to prepare DC-activated renal cancer antigen-specific CTLs. Magnetic beads were used to sort out MDSCs activated by the exosomes, and fluorescence staining with carboxyfluorescein diacetate succinimidyl ester (CFSE) and flow cytometry were performed to assess the inhibitory effect of activated MDSCs on the proliferation of CTLs. MDSCs, CTLs and Renca cells were co-cultured in vitro, and the inhibitory effect of exosomes-activated MDSCs on the killing activity of CTLs was observed using LDH release assay. Results Renca cell-derived exosomes effectively induced the aggregation of MDSCs. We successfully isolated DCs from the mice and obtained DC-activated renal cancer antigen-specific CTLs. Compared with the CTLs cultured alone or in the presence of unactivated MDSCs, the CTLs co-cultured with exosomes-activated MDSCs showed a significantly lower proliferation index and a lower killing rate against Renca cells (P < 0.05). Conclusion MDSCs activated by Renca cell-derived exosomes can inhibit the proliferation and lower the cell-killing efficiency of renal cancer antigen-specific CTLs in vitro, suggesting a significant role of MDSCs in immune escape of renal cancer.http://aammt.tmmu.edu.cn/Upload/rhtml/201811195.htmrenca cellsexosomesmyeloid-derived suppressor cellscytotoxic t lymphocytesinhibitory effect
spellingShingle XU Haoyu
WANG Hexi
LI Nan
ZHANG Yao
Inhibitory effect of myeloid-derived suppressor cells activated by Renca cell-derived exosomes on mouse cytotoxic T lymphocytes in vitro
Di-san junyi daxue xuebao
renca cells
exosomes
myeloid-derived suppressor cells
cytotoxic t lymphocytes
inhibitory effect
title Inhibitory effect of myeloid-derived suppressor cells activated by Renca cell-derived exosomes on mouse cytotoxic T lymphocytes in vitro
title_full Inhibitory effect of myeloid-derived suppressor cells activated by Renca cell-derived exosomes on mouse cytotoxic T lymphocytes in vitro
title_fullStr Inhibitory effect of myeloid-derived suppressor cells activated by Renca cell-derived exosomes on mouse cytotoxic T lymphocytes in vitro
title_full_unstemmed Inhibitory effect of myeloid-derived suppressor cells activated by Renca cell-derived exosomes on mouse cytotoxic T lymphocytes in vitro
title_short Inhibitory effect of myeloid-derived suppressor cells activated by Renca cell-derived exosomes on mouse cytotoxic T lymphocytes in vitro
title_sort inhibitory effect of myeloid derived suppressor cells activated by renca cell derived exosomes on mouse cytotoxic t lymphocytes in vitro
topic renca cells
exosomes
myeloid-derived suppressor cells
cytotoxic t lymphocytes
inhibitory effect
url http://aammt.tmmu.edu.cn/Upload/rhtml/201811195.htm
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AT wanghexi inhibitoryeffectofmyeloidderivedsuppressorcellsactivatedbyrencacellderivedexosomesonmousecytotoxictlymphocytesinvitro
AT linan inhibitoryeffectofmyeloidderivedsuppressorcellsactivatedbyrencacellderivedexosomesonmousecytotoxictlymphocytesinvitro
AT zhangyao inhibitoryeffectofmyeloidderivedsuppressorcellsactivatedbyrencacellderivedexosomesonmousecytotoxictlymphocytesinvitro