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Reprogramming of T cell-derived small extracellular vesicles using IL2 surface engineering induces potent anti-cancer effects through miRNA delivery

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dc.contributor.authorYoon, Jong Hyuk-
dc.date.accessioned2023-08-16T09:29:00Z-
dc.date.available2023-08-16T09:29:00Z-
dc.date.created2022-11-30-
dc.date.issued2022-12-
dc.identifier.issn2001-3078-
dc.identifier.urihttp://scholarworks.bwise.kr/kbri/handle/2023.sw.kbri/176-
dc.description.abstractT cell-derived small extracellular vesicles (sEVs) exhibit anti-cancer effects. However, their anti-cancer potential should be reinforced to enhance clinical applicability. Herein, we generated interleukin-2-tethered sEVs (IL2-sEVs) from engineered Jurkat T cells expressing IL2 at the plasma membrane via a flexible linker to induce an autocrine effect. IL2-sEVs increased the anti-cancer ability of CD8(+) T cells without affecting regulatory T (T-reg) cells and down-regulated cellular and exosomal PD-L1 expression in melanoma cells, causing their increased sensitivity to CD8(+) T cell-mediated cytotoxicity. Its effect on CD8(+) T and melanoma cells was mediated by several IL2-sEV-resident microRNAs (miRNAs), whose expressions were upregulated by the autocrine effects of IL2. Among the miRNAs, miR-181a-3p and miR-223-3p notably reduced the PD-L1 protein levels in melanoma cells. Interestingly, miR-181a-3p increased the activity of CD8(+) T cells while suppressing T-reg cell activity. IL2-sEVs inhibited tumour progression in melanoma-bearing immunocompetent mice, but not in immunodeficient mice. The combination of IL2-sEVs and existing anti-cancer drugs significantly improved anti-cancer efficacy by decreasing PD-L1 expression in vivo. Thus, IL2-sEVs are potential cancer immunotherapeutic agents that regulate both immune and cancer cells by reprogramming miRNA levels.-
dc.publisherCo-Action Publishing-
dc.titleReprogramming of T cell-derived small extracellular vesicles using IL2 surface engineering induces potent anti-cancer effects through miRNA delivery-
dc.typeArticle-
dc.contributor.affiliatedAuthorYoon, Jong Hyuk-
dc.identifier.doi10.1002/jev2.12287-
dc.identifier.wosid000892038100001-
dc.identifier.bibliographicCitationJournal of Extracellular Vesicles, v.11, no.12-
dc.relation.isPartOfJournal of Extracellular Vesicles-
dc.citation.titleJournal of Extracellular Vesicles-
dc.citation.volume11-
dc.citation.number12-
dc.type.rimsART-
dc.description.journalClass1-
dc.description.isOpenAccessY-
dc.description.journalRegisteredClassscie-
dc.description.journalRegisteredClassscopus-
dc.relation.journalResearchAreaCell Biology-
dc.relation.journalWebOfScienceCategoryCell Biology-
dc.subject.keywordPlusEXOSOMES-
dc.subject.keywordPlusMELANOMA-
dc.subject.keywordPlusINTERLEUKIN-2-
dc.subject.keywordPlusDACARBAZINE-
dc.subject.keywordPlusBIOGENESIS-
dc.subject.keywordPlusACTIVATION-
dc.subject.keywordPlusRECEPTORS-
dc.subject.keywordPlusIMMUNITY-
dc.subject.keywordPlusGROWTH-
dc.subject.keywordAuthorcancer-
dc.subject.keywordAuthorexosomal PD-L1-
dc.subject.keywordAuthorinterleukin-2-
dc.subject.keywordAuthorPD-L1-
dc.subject.keywordAuthorsmall extracellular vesicle-
dc.subject.keywordAuthorsmall extracellular vesicle engineering-
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연구본부 (퇴행성 뇌질환 연구그룹)
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