Tumor exosomes expressing Fas ligand mediate CD8+ T-cell apoptosis

Blood Cells Mol Dis. Sep-Oct 2005;35(2):169-73. doi: 10.1016/j.bcmd.2005.07.001.

Abstract

Tumor-derived immune suppression is considered to be a major mechanism of tumor evasion from the immune system destruction, however, little is known regarding the induction of T-cell functional suppression by tumor-derived exosomes. Herein, we investigate tumor-derived exosomes involved in normal immunological communications as means of inhibiting an antitumor T-cell response. Exosomes derived from LNCaP, a human prostate cancer cell line, were visualized by FACS and identified based on size (80-200 nm) in comparison to marker beads. Exosomes from tumor cell line inhibited T-cell proliferation. Dose-dependent apoptosis of T cells was induced by co-culture with tumor exosomes. Addition of anti-FasL antibody blocked the apoptosis induction by tumor exosomes. This study suggests that induction of T-cell apoptosis by tumor-derived exosomes appears to be a novel mechanism of tumor immune evasion.

MeSH terms

  • Antigens, Neoplasm / immunology
  • Antigens, Neoplasm / physiology
  • Apoptosis*
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Line, Tumor
  • Cell Proliferation
  • Coculture Techniques
  • Endosomes / immunology*
  • Endosomes / pathology
  • Fas Ligand Protein
  • Humans
  • Lymphocyte Activation
  • Male
  • Membrane Glycoproteins / physiology*
  • Prostatic Neoplasms / immunology
  • Prostatic Neoplasms / pathology*
  • Tumor Necrosis Factors / physiology*

Substances

  • Antigens, Neoplasm
  • FASLG protein, human
  • Fas Ligand Protein
  • Membrane Glycoproteins
  • Tumor Necrosis Factors