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

  • Nat Commun. 2018 Jan 30;9(1):435. doi: 10.1038/s41467-018-02865-1.
Naohiro Seo  1  2 ,  Yoshitaka Shirakura  3 ,  Yoshiro Tahara  4  5 ,  Fumiyasu Momose  3  4 ,  Naozumi Harada  3  4 ,  Hiroaki Ikeda  6 ,  Kazunari Akiyoshi  4  7 ,  Hiroshi Shiku  8  9
Affiliations
  • 1. Department of Immuno-Gene Therapy, Mie University Graduate School of Medicine, Edobashi, Tsu, Mie, 514-8507, Japan. [email protected].
  • 2. ERATO Bio-Nanotransporter Project, Japan Science and Technology Agency (JST), Kyoto, 615-8530, Japan. [email protected].
  • 3. Department of Immuno-Gene Therapy, Mie University Graduate School of Medicine, Edobashi, Tsu, Mie, 514-8507, Japan.
  • 4. ERATO Bio-Nanotransporter Project, Japan Science and Technology Agency (JST), Kyoto, 615-8530, Japan.
  • 5. Department of Applied Chemistry, Graduate School of Engineering, Kyushu University, Moto-oka, Fukuoka, 819-0395, Japan.
  • 6. Department of Oncology, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto, Nagasaki, 852-8523, Japan.
  • 7. Department of Polymer Chemistry, Graduate School of Engineering, Katsura Int'tech Center, Kyoto University, Nishikyo-ku, Kyoto, 615-8530, Japan.
  • 8. Department of Immuno-Gene Therapy, Mie University Graduate School of Medicine, Edobashi, Tsu, Mie, 514-8507, Japan. [email protected].
  • 9. ERATO Bio-Nanotransporter Project, Japan Science and Technology Agency (JST), Kyoto, 615-8530, Japan. [email protected].
PMID: 29382847 DOI: 10.1038/s41467-018-02865-1
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.

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