Activated CD8+ T cell extracellular vesicles prevent tumour progression by targeting of lesional mesenchymal cells

被引：178

作者：

Seo, Naohiro ^{[1
,2
]}

Shirakura, Yoshitaka ^{[1
]}

Tahara, Yoshiro ^{[2
,3
]}

Momose, Fumiyasu ^{[1
,2
]}

Harada, Naozumi ^{[1
,2
]}

Ikeda, Hiroaki ^{[4
]}

Akiyoshi, Kazunari ^{[2
,5
]}

Shiku, Hiroshi ^{[1
,2
]}

机构：

[1] Mie Univ, Grad Sch Med, Dept Immunogene Therapy, Tsu, Mie 5148507, Japan

[2] Japan Sci & Technol Agcy JST, ERATO Bionanotransporter Project, Kyoto 6158530, Japan

[3] Kyushu Univ, Grad Sch Engn, Dept Appl Chem, Fukuoka 8190395, Japan

[4] Nagasaki Univ, Grad Sch Biomed Sci, Dept Oncol, Nagasaki 8528523, Japan

[5] Kyoto Univ, Katsura Inttech Ctr, Grad Sch Engn, Dept Polymer Chem,Nishikyo Ku, Kyoto 6158530, Japan

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

基金：

日本科学技术振兴机构;

关键词：

ENDOTHELIAL PROGENITOR CELLS; BREAST-CANCER CELLS; BONE-MARROW; STEM-CELLS; MICROENVIRONMENTAL REGULATION; STROMAL CELLS; IN-VIVO; EXOSOMES; ADHESION; IMMUNOTHERAPY;

D O I：

10.1038/s41467-018-02865-1

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Fibroblastic tumour stroma comprising mesenchymal stem cells (MSCs) and cancer-associated fibroblasts (CAFs) promotes the invasive and metastatic properties of tumour cells. Here we show that activated CD8(+) T cell-derived extracellular vesicles (EVs) interrupt fibroblastic stroma-mediated tumour progression. Activated CD8(+) T cells from healthy mice transiently release cytotoxic EVs causing marked attenuation of tumour invasion and metastasis by apoptotic depletion of mesenchymal tumour stromal cells. Infiltration of EV-producing CD8(+) T cells is observed in neovascular areas with high mesenchymal cell density, and tumour MSC depletion is associated with preferential engulfment of CD8(+) T cell EVs in this setting. Thus, CD8(+) T cells have the capacity to protect tumour progression by EV-mediated depletion of mesenchymal tumour stromal cells in addition to their conventional direct cytotoxicity against tumour cells.

引用

页数：11

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