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Exosomes derived from Rab27aoverexpressing tumor cells elicit efficient induction of antitumor immunity

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Lung cancer is the leading cause of mortality worldwide. However, there is a lack of effective therapeutic strategies. Currently, tumor immunotherapy based on exosomes, which are secreted by a variety of cell types including tumor cells, has drawn particular attention and are suggested to have the potential for exploitation in tumor therapy. Nevertheless, the therapeutic efficacy mediated via tumor cellderived exosomes is not satisfactory. Rab27a, one of the Rab family of small GTPases, has been suggested to be important in exosome secretion. Thus, the purpose of the present study was to examine whether exosomes derived from Rab27aoverexpressing cells elicited more potent antitumor immunity. A Rab27aoverexpressing line was established via transfection of a Rab27a overexpression vector into the human nonsmallcell lung cancer cell line, A549. Exosomes were isolated and the typical exosomal protein markers, CD9, CD63, heat shock protein (Hsp) 70 and Hsp90, were found to be enriched in the exosomes derived from Rab27aoverexpressing cells. Subsequently, these exosomes were demonstrated to be capable of upregulating major histocompatibility complex class II molecules as well as the costimulatory molecules CD80 and CD86 on dendritic cells (DCs), suggesting that more potent maturation of DCs was induced. Furthermore, DCs loaded with exosomes derived from Rab27overexpressing cells significantly promoted CD4+ T cell proliferation in vitro. In addition, in vivo immunization of exosomes derived from Rab27aoverexpressing cells inhibited tumor growth in a mouse model. It was also demonstrated that splenocytes from mice immunized with exosomes derived from Rab27overexpressing cells expressed high levels of type I cytokines, including IL2 and IFNγ, which are important in the regulation of cellmediated antitumor immunity. Collectively, it was demonstrated that exosomes derived from Rab27aoverexpressing cancer cells elicited more potent antitumor immune effects, which may provide novel insights for the development of efficient exosomebased cancer vaccines.
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Document Type: Research Article

Affiliations: 1: Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China 2: Department of Respiratory Medicine, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China 3: Department of Orthopaedic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China

Publication date: January 1, 2013

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  • Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
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