Immune modulation of T-cell and NK (natural killer) cell activities by TEXs (tumour-derived exosomes)
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TLDR
Correlations between the TEX molecular profile or TEX protein levels and clinical data in cancer patients suggest that TEX-mediated effects on immune cells are prognostically important.Abstract:
Body fluids of cancer patients contain TEXs (tumour-derived exosomes). Tumours release large quantities of TEXs, and the protein content of exosome or MV (microvesicle) fractions isolated from patients’ sera is high. TEXs down-regulate functions of immune cells, thus promoting tumour progression. We isolated TEXs from tumour cell supernatants and sera of patients with solid tumours or AML (acute myelogenous leukaemia). The molecular profile of TEXs was distinct from that of circulating exosomes derived from normal cells. TEXs were co-incubated with activated T-cells, conventional CD4 + CD25 neg T-cells or CD56 + CD16 + NK (natural killer) cells respectively. TEXs down-regulated CD3ζ and JAK3 (Janus kinase 3) expression in primary activated T-cells and mediated Fas/FasL (Fas ligand)-driven apoptosis of CD8 + T-cells. TEXs promoted CD4 + CD25 neg T-cell proliferation and their conversion into CD4 + CD25 hi FOXP3 + (FOXP3 is forkhead box P3) Treg cells (regulatory T-cells), which also expressed IL-10 (interleukin 10), TGFβ1 (transforming growth factor β1), CTLA-4 (cytotoxic T-lymphocyte antigen 4), GrB (granzyme B)/perforin and effectively mediated suppression. Neutralizing antibodies specific for TGFβ1 and/or IL-10 inhibited the ability of TEXs to expand Treg cells. TEXs obtained at diagnosis from AML patients’ sera were positive for blast-associated markers CD33, CD34, CD117 and TGFβ1, and they decreased cytotoxic activity of NK cells isolated from NC (normal control) donors, induced Smad phosphorylation and down-regulated NKG2D receptor expression. Correlations between the TEX molecular profile or TEX protein levels and clinical data in cancer patients suggest that TEX-mediated effects on immune cells are prognostically important. In contrast with exosomes released by normal cells, TEXs have immunosuppressive properties and are involved in regulating peripheral tolerance in patients with cancer.read more
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References
More filters
Journal ArticleDOI
The blockade of immune checkpoints in cancer immunotherapy
TL;DR: Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1 (PD1), indicate broad and diverse opportunities to enhance antitumour immunity with the potential to produce durable clinical responses.
Journal ArticleDOI
Exosomes: composition, biogenesis and function
TL;DR: The physical properties that define exosomes as a specific population of secreted vesicles are described, their biological effects, particularly on the immune system, are summarized, and the potential roles that secretedvesicles could have as intercellular messengers are discussed.
Journal ArticleDOI
Membrane vesicles as conveyors of immune responses
TL;DR: The role of membrane vesicles, in particular exosomes, in the communication between immune cells, and between tumour and immune cells is focused on.
Journal ArticleDOI
Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET
Héctor Peinado,Maša Alečković,Simon Lavotshkin,Irina Matei,Bruno Costa-Silva,Gema Moreno-Bueno,Marta Hergueta-Redondo,Caitlin Williams,Guillermo García-Santos,Cyrus M. Ghajar,Ayuko Nitadori-Hoshino,Caitlin Hoffman,Karen Badal,Benjamin A. Garcia,Margaret K. Callahan,Jianda Yuan,Vilma R. Martins,Johan Skog,Rosandra N. Kaplan,Mary S. Brady,Jedd D. Wolchok,Jedd D. Wolchok,Paul B. Chapman,Paul B. Chapman,Yibin Kang,Yibin Kang,Jacqueline Bromberg,Jacqueline Bromberg,David Lyden +28 more
TL;DR: The data show that exosome production, transfer and education of bone marrow cells supports tumor growth and metastasis, has prognostic value and offers promise for new therapeutic directions in the metastatic process.
Journal ArticleDOI
Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression
Silvia Deaglio,Karen M. Dwyer,Wenda Gao,David J. Friedman,Anny Usheva,Anna Erat,Jiang-Fan Chen,Keiichii Enjyoji,Joel Linden,Mohamed Oukka,Vijay K. Kuchroo,Terry B. Strom,Simon C. Robson +12 more
TL;DR: It is concluded that CD39 and CD73 are surface markers of T reg cells that impart a specific biochemical signature characterized by adenosine generation that has functional relevance for cellular immunoregulation.
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