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

• Seo, Naohiro

  Department of Immuno-Gene Therapy, Mie University Graduate School of Medicine･ERATO Bio-Nanotransporter Project, Japan Science and Technology Agency (JST)

• Shirakura, Yoshitaka

  Department of Immuno-Gene Therapy, Mie University Graduate School of Medicine

• Tahara, Yoshiro

  ERATO Bio-Nanotransporter Project, Japan Science and Technology Agency (JST)･Department of Applied Chemistry, Graduate School of Engineering, Kyushu University

• Momose, Fumiyasu

  Department of Immuno-Gene Therapy, Mie University Graduate School of Medicine･ERATO Bio-Nanotransporter Project, Japan Science and Technology Agency (JST)

• Harada, Naozumi

  Department of Immuno-Gene Therapy, Mie University Graduate School of Medicine･ERATO Bio-Nanotransporter Project, Japan Science and Technology Agency (JST)

• Ikeda, Hiroaki

  Department of Oncology, Nagasaki University Graduate School of Biomedical Sciences

• Akiyoshi, Kazunari

  ERATO Bio-Nanotransporter Project, Japan Science and Technology Agency (JST)･Department of Polymer Chemistry, Graduate School of Engineering, Katsura Int’tech Center, Kyoto University

• Shiku, Hiroshi

  Department of Immuno-Gene Therapy, Mie University Graduate School of Medicine･ERATO Bio-Nanotransporter Project, Japan Science and Technology Agency (JST)

Abstract

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.

Journal

• Nature Communications

  Nature Communications 9 435-, 2018-01-30

  Springer Nature

Keywords

• General Physics and Astronomy
• General Biochemistry, Genetics and Molecular Biology
• General Chemistry
• Multidisciplinary

Details

• CRID: 1050282813184439680
• NII Article ID: 120006532079
• ISSN: 20411723
• DOI: 10.1038/s41467-018-02865-1
• HANDLE: 2433/234716
• Web Site: https://www.nature.com/articles/s41467-018-02865-1
• Web Site: https://www.nature.com/articles/s41467-018-02865-1.pdf
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN