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

Naohiro Seo (), Yoshitaka Shirakura, Yoshiro Tahara, Fumiyasu Momose, Naozumi Harada, Hiroaki Ikeda, Kazunari Akiyoshi and Hiroshi Shiku ()
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Naohiro Seo: Mie University Graduate School of Medicine
Yoshitaka Shirakura: Mie University Graduate School of Medicine
Yoshiro Tahara: Japan Science and Technology Agency (JST)
Fumiyasu Momose: Mie University Graduate School of Medicine
Naozumi Harada: Mie University Graduate School of Medicine
Hiroaki Ikeda: Nagasaki University Graduate School of Biomedical Sciences
Kazunari Akiyoshi: Japan Science and Technology Agency (JST)
Hiroshi Shiku: Mie University Graduate School of Medicine

Nature Communications, 2018, vol. 9, issue 1, 1-11

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-02865-1

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