title: Activated T cell exosomes promote tumor invasion via Fas signaling pathway.
abstract: Activated T cells release bioactive Fas ligand (FasL) in exosomes, which subsequently induce self-apoptosis of T cells. However, their potential effects on cell apoptosis in tumors are still unknown. In this study, we purified exosomes expressing FasL from activated CD8(+) T cell from OT-I mice and found that activated T cell exosomes had little effect on apoptosis and proliferation of tumor cells but promoted the invasion of B16 and 3LL cancer cells in vitro via the Fas/FasL pathway. Activated T cell exosomes increased the amount of cellular FLICE inhibitory proteins and subsequently activated the ERK and NF-κB pathways, which subsequently increased MMP9 expression in the B16 murine melanoma cells. In a tumor-invasive model in vivo, we observed that the activated T cell exosomes promoted the migration of B16 tumor cells to lung. Interestingly, pretreatment with FasL mAb significantly reduced the migration of B16 tumor cells to lung. Furthermore, CD8 and FasL double-positive exosomes from tumor mice, but not normal mice, also increased the expression of MMP9 and promoted the invasive ability of B16 murine melanoma and 3LL lung cancer cells. In conclusion, our results indicate that activated T cell exosomes promote melanoma and lung cancer cell metastasis by increasing the expression of MMP9 via Fas signaling, revealing a new mechanism of tumor immune escape.
authors.affiliation: Institute of Immunology, School of Medicine, Zhejiang University, Hangzhou 310058, Zhejiang, China.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Cai
authors.forename: Fei
authors.initials: F
authors.lastname: Yang
authors.forename: Lei
authors.initials: L
authors.lastname: Yu
authors.forename: Zhou
authors.initials: Z
authors.lastname: Yu
authors.forename: Lingling
authors.initials: L
authors.lastname: Jiang
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Wang
authors.forename: Yunshan
authors.initials: Y
authors.lastname: Yang
authors.forename: Lie
authors.initials: L
authors.lastname: Wang
authors.forename: Xuetao
authors.initials: X
authors.lastname: Cao
authors.forename: Jianli
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D055354:Exosomes / Q000276:immunology / Q000378:metabolism*; D053222:Fas Ligand Protein / Q000276:immunology / Q000378:metabolism*; D005434:Flow Cytometry; D008213:Lymphocyte Activation / Q000276:immunology; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D009361:Neoplasm Invasiveness / Q000276:immunology* / Q000473:pathology; D009374:Neoplasms, Experimental / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D019139:Tumor Escape / Q000276:immunology*; D015854:Up-Regulation
chemical_list: D053222:Fas Ligand Protein; D020780:Matrix Metalloproteinase 9