共 40 条
Plasma Gelsolin Inhibits CD8+ T-cell Function and Regulates Glutathione Production to Confer Chemoresistance in Ovarian Cancer
被引:45
作者:

Asare-Werehene, Meshach
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h-index: 0
机构:
Univ Ottawa, Dept Obstet & Gynecol, Ottawa, ON, Canada
Ottawa Hosp Res Inst, Chron Dis Program, Ottawa, ON, Canada
Univ Montreal, CHUM, Ctr Rech, Montreal, PQ, Canada Univ Ottawa, Dept Obstet & Gynecol, Ottawa, ON, Canada

Communal, Laudine
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h-index: 0
机构:
Univ Montreal, Inst Canc Montreal, Dept Med, Montreal, PQ, Canada Univ Ottawa, Dept Obstet & Gynecol, Ottawa, ON, Canada

Carmona, Euridice
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h-index: 0
机构:
Univ Montreal, Inst Canc Montreal, Dept Med, Montreal, PQ, Canada Univ Ottawa, Dept Obstet & Gynecol, Ottawa, ON, Canada

Han, Youngjin
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h-index: 0
机构:
Seoul Natl Univ, Coll Med, Canc Res Inst, Seoul, South Korea
Seoul Natl Univ, Dept Obstet & Gynecol, Coll Med, Seoul, South Korea Univ Ottawa, Dept Obstet & Gynecol, Ottawa, ON, Canada

Song, Yong Sang
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h-index: 0
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Seoul Natl Univ, Coll Med, Canc Res Inst, Seoul, South Korea
Seoul Natl Univ, Dept Obstet & Gynecol, Coll Med, Seoul, South Korea Univ Ottawa, Dept Obstet & Gynecol, Ottawa, ON, Canada

Burger, Dylan
论文数: 0 引用数: 0
h-index: 0
机构:
Ottawa Hosp Res Inst, Chron Dis Program, Ottawa, ON, Canada
Univ Montreal, CHUM, Ctr Rech, Montreal, PQ, Canada
Univ Montreal, Inst Canc Montreal, Dept Med, Montreal, PQ, Canada Univ Ottawa, Dept Obstet & Gynecol, Ottawa, ON, Canada

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Tsang, Benjamin K.
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h-index: 0
机构:
Univ Ottawa, Dept Obstet & Gynecol, Ottawa, ON, Canada
Ottawa Hosp Res Inst, Chron Dis Program, Ottawa, ON, Canada
Univ Montreal, CHUM, Ctr Rech, Montreal, PQ, Canada
Univ Ottawa, Dept Cellular & Mol Med, Ottawa, ON, Canada
Univ Ottawa, Ctr Infect Immun & Inflammat, Ottawa, ON, Canada Univ Ottawa, Dept Obstet & Gynecol, Ottawa, ON, Canada
机构:
[1] Univ Ottawa, Dept Obstet & Gynecol, Ottawa, ON, Canada
[2] Ottawa Hosp Res Inst, Chron Dis Program, Ottawa, ON, Canada
[3] Univ Montreal, CHUM, Ctr Rech, Montreal, PQ, Canada
[4] Univ Montreal, Inst Canc Montreal, Dept Med, Montreal, PQ, Canada
[5] Seoul Natl Univ, Coll Med, Canc Res Inst, Seoul, South Korea
[6] Seoul Natl Univ, Dept Obstet & Gynecol, Coll Med, Seoul, South Korea
[7] Univ Ottawa, Dept Cellular & Mol Med, Ottawa, ON, Canada
[8] Univ Ottawa, Ctr Infect Immun & Inflammat, Ottawa, ON, Canada
基金:
加拿大健康研究院;
关键词:
CHEMOTHERAPY;
PROTEIN;
D O I:
10.1158/0008-5472.CAN-20-0788
中图分类号:
R73 [肿瘤学];
学科分类号:
100214 ;
摘要:
Although initial treatment of ovarian cancer is successful, tumors typically relapse and become resistant to treatment. Because of poor infiltration of effector T cells, patients are mostly unresponsive to immunotherapy. Plasma gelsolin (pGSN) is transported by exosomes (small extracellular vesicle, sEV) and plays a key role in ovarian cancer chemoresistance, yet little is known about its role in immunosurveillance. Here, we report the immunomodulatory roles of sEV-pGSN in ovarian cancer chemoresistance. In chemosensitive conditions, secretion of sEV-pGSN was low, allowing for optimal CD8(+) T-cell function. This resulted in increased T-cell secretion of IFN gamma, which reduced intracellular glutathione (GSH) production and sensitized chemosensitive cells to cis-diaminedichloroplatinum (CDDP)-induced apoptosis. In chemoresistant conditions, increased secretion of sEV-pGSN by ovarian cancer cells induced apoptosis in CD8(+) T cells. IFN gamma secretion was therefore reduced, resulting in high GSH production and resistance to CDDP-induced death in ovarian cancer cells. These findings support our hypothesis that sEV-pGSN attenuates immunosurveillance and regulates GSH biosynthesis, a phenomenon that contributes to chemoresistance in ovarian cancer. Significance: These findings provide new insight into pGSNmediated immune cell dysfunction in ovarian cancer chemoresistance and demonstrate how this dysfunction can be exploited to enhance immunotherapy.
引用
收藏
页码:3959 / 3971
页数:13
相关论文
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Chou, Ming-Chih
.
ONCOTARGET,
2017, 8 (44)
:77152-77167

Chen, Chun-Chi
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机构:
Chung Shan Med Univ, Inst Med, Taichung, Taiwan
Changhua Christian Hosp, Dept Surg, Sect Urol, Changhua, Taiwan Chung Shan Med Univ, Inst Med, Taichung, Taiwan

Chiou, Shiow-Her
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机构:
Natl Chung Hsing Univ, Grad Inst Microbiol & Publ Hlth, Taichung, Taiwan Chung Shan Med Univ, Inst Med, Taichung, Taiwan

Yang, Cheng-Lin
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机构:
Natl Chung Hsing Univ, Grad Inst Biomed Sci, Taichung, Taiwan Chung Shan Med Univ, Inst Med, Taichung, Taiwan

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Lin, Tze-Yi
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机构:
China Med Univ, China Med Univ Hosp, Dept Pathol, Taichung, Taiwan Chung Shan Med Univ, Inst Med, Taichung, Taiwan

Chang, Hui-Wen
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机构:
China Med Univ, China Med Univ Hosp, Dept Pathol, Taichung, Taiwan Chung Shan Med Univ, Inst Med, Taichung, Taiwan

You, Weir-Chiang
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机构:
Taichung Vet Gen Hosp, Dept Radiat Oncol, Taichung, Taiwan Chung Shan Med Univ, Inst Med, Taichung, Taiwan

Huang, Hisu-Wen
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机构:
Council Agr, Endem Species Res Inst, Execut Yuan, Chi Chi, Taiwan Chung Shan Med Univ, Inst Med, Taichung, Taiwan

Chen, Chien-Min
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Council Agr, Endem Species Res Inst, Execut Yuan, Chi Chi, Taiwan Chung Shan Med Univ, Inst Med, Taichung, Taiwan

Chen, Nien-Cheng
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机构:
Chung Shan Med Univ, Inst Biochem Microbiol & Immunol, Taichung, Taiwan Chung Shan Med Univ, Inst Med, Taichung, Taiwan

Chou, Fen-Pi
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机构:
Chung Shan Med Univ, Inst Biochem Microbiol & Immunol, Taichung, Taiwan Chung Shan Med Univ, Inst Med, Taichung, Taiwan

Chou, Ming-Chih
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机构:
Chung Shan Med Univ, Inst Med, Taichung, Taiwan
Chung Shan Med Univ, Chung Shan Med Univ Hosp, Dept Family & Community Med, Taichung, Taiwan Chung Shan Med Univ, Inst Med, Taichung, Taiwan