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

• Published in: Nature communications Vol. 9; no. 1; pp. 435 - 11
• Main Authors: Seo, Naohiro, Shirakura, Yoshitaka, Tahara, Yoshiro, Momose, Fumiyasu, Harada, Naozumi, Ikeda, Hiroaki, Akiyoshi, Kazunari, Shiku, Hiroshi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30.01.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/1; 13/31; 13/51; 14; 14/19; 14/63; 631/250/580/1884; 631/80/82/23; Apoptosis; Cancer; CD8 antigen; Cell density; Cytotoxicity; Depletion; Extracellular vesicles; Fibroblasts; Humanities and Social Sciences; Infiltration; Invasiveness; Lymphocytes; Lymphocytes T; Mesenchyme; Metastases; multidisciplinary; Science; Science (multidisciplinary); Stem cell transplantation; Stem cells; Stromal cells; Toxicity; Tumors; Vesicles
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-02865-1

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. Immune cells have an important role in tumour progression. Here, the authors show that extracellular vesicles from activated CD8 + T cells attenuate tumour progression by depletion of mesenchymal tumour stromal cells.