title: Exosomes from M1-Polarized Macrophages Potentiate the Cancer Vaccine by Creating a Pro-inflammatory Microenvironment in the Lymph Node.
abstract: Exosomes are small membrane-bound vesicular particles generated by most cells for intercellular communication and regulation. During biogenesis, specific lipids, RNAs, proteins, and carbohydrates are enriched and packaged into the vesicles so that the exosomal contents reflect not only the source but also the physiological conditions of the parental cells. These exosomes transport materials or signals to the target cells for diverse physiological purposes. Our study focused on the exosomes derived from M1-polarized, proinflammatory macrophages for the possibility of using M1 exosomes as an immunopotentiator for a cancer vaccine. The M1 exosomes displayed a tropism toward lymph nodes after subcutaneous injection, primarily taken up by the local macrophages and dendritic cells, and they induced the release of a pool of Th1 cytokines. We found that M1, but not M2, exosomes enhanced activity of lipid calcium phosphate (LCP) nanoparticle-encapsulated Trp2 vaccine, and they induced a stronger antigen-specific cytotoxic T cell response. The M1 exosomes proved to be a more potent immunopotentiator than CpG oligonucleotide when used with LCP nanoparticle vaccine in a melanoma growth inhibition study. Thus, our study indicated that exosomes derived from M1-polarized macrophages could be used as a vaccine adjuvant.
authors.affiliation: Division of Molecular Pharmaceutics and Center for Nanotechnology in Drug Delivery, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Pharmaceutics, School of Pharmaceutical Sciences, Soochow University, Suzhou 215123, Jiangsu, China.
authors.forename: Lifang
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Division of Molecular Pharmaceutics and Center for Nanotechnology in Drug Delivery, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Division of Molecular Pharmaceutics and Center for Nanotechnology in Drug Delivery, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: leafh@unc.edu.
authors.forename: Leaf
authors.initials: L
authors.lastname: Huang
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D002130:Calcium Phosphates / Q000737:chemistry; D019496:Cancer Vaccines / Q000008:administration & dosage*; D004337:Drug Carriers; D004339:Drug Compounding; D055354:Exosomes / Q000737:chemistry* / Q000276:immunology; D005260:Female; D015870:Gene Expression; D007155:Immunologic Factors / Q000737:chemistry / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000276:immunology; D008198:Lymph Nodes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008546:Melanoma, Experimental / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D012878:Skin Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D002130:Calcium Phosphates; D019496:Cancer Vaccines; D004337:Drug Carriers; D007155:Immunologic Factors; D009363:Neoplasm Proteins; D009838:Oligodeoxyribonucleotides; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase; C018392:tricalcium phosphate
keywords: cancer vaccine; exosome; nanoparticle; tumor microenvironment