Systemic T Cells Immunosuppression of Glioma Stem Cell-Derived Exosomes Is Mediated by Monocytic Myeloid-Derived Suppressor Cells
Publication Date
January 20, 2017
Authors
Rossana Domenis, Daniela Cesselli, Barbara Toffoletto, Evgenia Bourkoula, et al
Volume
12
Issue
1
Pages
e0169932
DOI
https://dx.plos.org/10.1371/journal.pone.0169932
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0169932
Scopus
85010469830
Mendeley
http://www.mendeley.com/research/systemic-t-cells-immunosuppression-glioma-stem-cellderived-exosomes-mediated-monocytic-myeloidderive
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{"title"=>"Systemic T cells immunosuppression of glioma stem cell-derived exosomes is mediated by monocytic myeloid-derived suppressor cells", "type"=>"journal", "authors"=>[{"first_name"=>"Rossana", "last_name"=>"Domenis", "scopus_author_id"=>"14819050200"}, {"first_name"=>"Daniela", "last_name"=>"Cesselli", "scopus_author_id"=>"6507233576"}, {"first_name"=>"Barbara", "last_name"=>"Toffoletto", "scopus_author_id"=>"26638542300"}, {"first_name"=>"Evgenia", "last_name"=>"Bourkoula", "scopus_author_id"=>"56121495700"}, {"first_name"=>"Federica", "last_name"=>"Caponnetto", "scopus_author_id"=>"56122425100"}, {"first_name"=>"Ivana", "last_name"=>"Manini", "scopus_author_id"=>"16239385400"}, {"first_name"=>"Antonio Paolo", "last_name"=>"Beltrami", "scopus_author_id"=>"15070243200"}, {"first_name"=>"Tamara", "last_name"=>"Ius", "scopus_author_id"=>"15725154500"}, {"first_name"=>"Miran", "last_name"=>"Skrap", "scopus_author_id"=>"6701507303"}, {"first_name"=>"Carla", "last_name"=>"Di Loreto", "scopus_author_id"=>"57200902538"}, {"first_name"=>"Giorgia", "last_name"=>"Gri", "scopus_author_id"=>"6602912853"}], "year"=>2017, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "isbn"=>"1111111111", "pmid"=>"28107450", "scopus"=>"2-s2.0-85010469830", "doi"=>"10.1371/journal.pone.0169932", "sgr"=>"85010469830", "pui"=>"614169813"}, "id"=>"2b5e16d6-a3f3-37bf-ba97-24c720777aac", "abstract"=>"A major contributing factor to glioma development and progression is its ability to evade the immune system. Nano-meter sized vesicles, exosomes, secreted by glioma-stem cells (GSC) can act as mediators of intercellular communication to promote tumor immune escape. Here, we investigated the immunomodulatory properties of GCS-derived exosomes on different peripheral immune cell populations. Healthy donor peripheral blood mononuclear cells (PBMCs) stimulated with anti-CD3, anti-CD28 and IL-2, were treated with GSC-derived exosomes. Phenotypic characterization, cell proliferation, Th1/Th2 cytokine secretion and intracellular cytokine production were analysed by distinguishing among effector T cells, regulatory T cells and monocytes. In unfractionated PBMCs, GSC-derived exosomes inhibited T cell activation (CD25 and CD69 expression), proliferation and Th1 cytokine production, and did not affect cell viability or regulatory T-cell suppression ability. Furthermore, exosomes were able to enhance proliferation of purified CD4+ T cells. In PBMCs culture, glioma-derived exosomes directly promoted IL-10 and arginase-1 production and downregulation of HLA-DR by unstimulated CD14+ monocytic cells, that displayed an immunophenotype resembling that of monocytic myeloid-derived suppressor cells (Mo-MDSCs). Importantly, the removal of CD14+ monocytic cell fraction from PBMCs restored T-cell proliferation. The same results were observed with exosomes purified from plasma of glioblastoma patients. Our results indicate that glioma-derived exosomes suppress T-cell immune response by acting on monocyte maturation rather than on direct interaction with T cells. Selective targeting of Mo-MDSC to treat glioma should be considered with regard to how immune cells allow the acquirement of effector functions and therefore counteracting tumor progression.", "link"=>"http://www.mendeley.com/research/systemic-t-cells-immunosuppression-glioma-stem-cellderived-exosomes-mediated-monocytic-myeloidderive", "reader_count"=>43, "reader_count_by_academic_status"=>{"Unspecified"=>3, "Professor > Associate Professor"=>2, "Researcher"=>8, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>2, "Student > Master"=>6, "Other"=>4, "Student > Bachelor"=>6, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>3, "Professor > Associate Professor"=>2, "Researcher"=>8, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>2, "Student > Master"=>6, "Other"=>4, "Student > Bachelor"=>6, "Lecturer > Senior Lecturer"=>1, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>4, "Engineering"=>2, "Biochemistry, Genetics and Molecular Biology"=>11, "Agricultural and Biological Sciences"=>8, "Medicine and Dentistry"=>13, "Psychology"=>2, "Immunology and Microbiology"=>3}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>2}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>13}, "Psychology"=>{"Psychology"=>2}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>8}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>11}, "Unspecified"=>{"Unspecified"=>4}}, "reader_count_by_country"=>{"Denmark"=>1}, "group_count"=>1}

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