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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / cytology*
  • Cell Line, Tumor
  • Cell Survival
  • Cells, Cultured
  • Extracellular Vesicles / physiology*
  • Extracellular Vesicles / transplantation
  • Female
  • Mesenchymal Stem Cells / immunology
  • Mesenchymal Stem Cells / pathology*
  • Mice, Inbred BALB C
  • Neoplasms, Experimental / pathology
  • Neoplasms, Experimental / therapy*