Extracellular vesicles produced by immunomodulatory cells harboring OX40 ligand and 4-1BB ligand enhance antitumor immunity
Autor: | Soledad Palameta, Isadora Ferraz Semionatto, Jessica M. Toscaro, Adriana Franco Paes Leme, Andrea J. Manrique-Rincón, Luciana P. Ruas, Marcio C. Bajgelman |
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Rok vydání: | 2020 |
Předmět: |
CD4-Positive T-Lymphocytes
0301 basic medicine T cell Melanoma Experimental lcsh:Medicine Antigen-Presenting Cells OX40 Ligand Cancer immunotherapy In Vitro Techniques Lymphocyte Activation Cancer Vaccines Article Extracellular Vesicles Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Immune system Microscopy Electron Transmission Cell Line Tumor medicine Animals Immunologic Factors lcsh:Science education Transcription factor education.field_of_study Multidisciplinary lcsh:R Immunosurveillance FOXP3 Forkhead Transcription Factors OX40 ligand Genetically modified organism Mice Inbred C57BL 4-1BB Ligand 030104 developmental biology 4-1BB ligand medicine.anatomical_structure chemistry Cell culture 030220 oncology & carcinogenesis Cancer research lcsh:Q |
Zdroj: | Scientific Reports Scientific Reports, Vol 10, Iss 1, Pp 1-10 (2020) |
ISSN: | 2045-2322 |
Popis: | Genetically modified tumor cells harboring immunomodulators may be used as therapeutic vaccines to stimulate antitumor immunity. The therapeutic benefit of these tumor vaccines is extensively investigated and mechanisms by which they boost antitumor response may be further explored. Tumor cells are large secretors of extracellular vesicles (EVs). These EVs are able to vehiculate RNA and proteins to target cells, and engineered EVs also vehiculate recombinant proteins. In this study, we explore immunomodulatory properties of EVs derived from antitumor vaccines expressing the TNFSF ligands 4-1BBL and OX40L, modulating immune response mediated by immune cells and eliminating tumors. Our results suggest that the EVs secreted by genetically modified tumor cells harboring TNFSF ligands can induce T cell proliferation, inhibit the transcription factor FoxP3, associated with the maintenance of Treg phenotype, and enhance antitumor activity mediated by immune cells. The immunomodulatory extracellular vesicles have potential to be further engineered for developing new approaches for cancer therapy. |
Databáze: | OpenAIRE |
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