Tumor exosomes expressing Fas ligand mediate CD8+ T-cell apoptosis.
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.
Abusamra
Ashraf J
AJ
London Health Science Centers, London, Ontario, Canada.
Zhong
Zhaohui
Z
Zheng
Xiufen
X
Li
Mu
M
Ichim
Thomas E
TE
Chin
Joseph L
JL
Min
Wei-Ping
WP
D000951:Antigens, Neoplasm / Q000276:immunology / Q000502:physiology; D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018920:Coculture Techniques; D011992:Endosomes / Q000276:immunology* / Q000473:pathology; D053222:Fas Ligand Protein; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000276:immunology / Q000473:pathology*; D048069:Tumor Necrosis Factors / Q000502:physiology*
D000951:Antigens, Neoplasm; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D048069:Tumor Necrosis Factors