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Article: Exosomes derived from Vδ2-T cells control Epstein-Barr virus-associated tumors and induce T cell antitumor immunity

TitleExosomes derived from Vδ2-T cells control Epstein-Barr virus-associated tumors and induce T cell antitumor immunity
Authors
Issue Date2020
PublisherAmerican Association for the Advancement of Science. The Journal's web site is located at http://www.sciencemag.org/marketing/stm/
Citation
Science Translational Medicine, 2020, v. 12 n. 563, p. article no. eaaz3426 How to Cite?
AbstractTreatment of life-threatening Epstein-Barr virus (EBV)–associated tumors remains a great challenge, especially for patients with relapsed or refractory disease. Here, we found that exosomes derived from phosphoantigen-expanded Vδ2-T cells (Vδ2-T-Exos) contained death-inducing ligands (FasL and TRAIL), an activating receptor for natural killer (NK) cells (NKG2D), immunostimulatory ligands (CD80 and CD86), and antigen-presenting molecules (MHC class I and II). Vδ2-T-Exos targeted and efficiently killed EBV-associated tumor cells through FasL and TRAIL pathways and promoted EBV antigen–specific CD4 and CD8 T cell expansion. Administration of Vδ2-T-Exos effectively controlled EBV-associated tumors in Rag2−/−γc−/− and humanized mice. Because expanding Vδ2-T cells and preparing autologous Vδ2-T-Exos from cancer patients ex vivo in large scale is challenging, we explored the antitumor activity of allogeneic Vδ2-T-Exos in humanized mouse cancer models. Here, we found that allogeneic Vδ2-T-Exos had more effective antitumor activity than autologous Vδ2-T-Exos in humanized mice; the allogeneic Vδ2-T-Exos increased the infiltration of T cells into tumor tissues and induced more robust CD4 and CD8 T cell–mediated antitumor immunity. Compared with exosomes derived from NK cells (NK-Exos) with direct cytotoxic antitumor activity or dendritic cells (DC-Exos) that induced T cell antitumor responses, Vδ2-T-Exos directly killed tumor cells and induced T cell–mediated antitumor response, thus resulting in more effective control of EBV-associated tumors. This study provided proof of concept for the strategy of using Vδ2-T-Exos, especially allogeneic Vδ2-T-Exos, to treat EBV-associated tumors.
Persistent Identifierhttp://hdl.handle.net/10722/288126
ISSN
2020 SCImago Journal Rankings: 6.819
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWang, X-
dc.contributor.authorXiang, Z-
dc.contributor.authorHUANG, C-
dc.contributor.authorPei, Y-
dc.contributor.authorWang, X-
dc.contributor.authorZhi, H-
dc.contributor.authorWong, WHS-
dc.contributor.authorWei, H-
dc.contributor.authorNg, IOL-
dc.contributor.authorLee, PPW-
dc.contributor.authorChan, GCF-
dc.contributor.authorLau, YL-
dc.contributor.authorTu, W-
dc.date.accessioned2020-10-05T12:08:15Z-
dc.date.available2020-10-05T12:08:15Z-
dc.date.issued2020-
dc.identifier.citationScience Translational Medicine, 2020, v. 12 n. 563, p. article no. eaaz3426-
dc.identifier.issn1946-6242-
dc.identifier.urihttp://hdl.handle.net/10722/288126-
dc.description.abstractTreatment of life-threatening Epstein-Barr virus (EBV)–associated tumors remains a great challenge, especially for patients with relapsed or refractory disease. Here, we found that exosomes derived from phosphoantigen-expanded Vδ2-T cells (Vδ2-T-Exos) contained death-inducing ligands (FasL and TRAIL), an activating receptor for natural killer (NK) cells (NKG2D), immunostimulatory ligands (CD80 and CD86), and antigen-presenting molecules (MHC class I and II). Vδ2-T-Exos targeted and efficiently killed EBV-associated tumor cells through FasL and TRAIL pathways and promoted EBV antigen–specific CD4 and CD8 T cell expansion. Administration of Vδ2-T-Exos effectively controlled EBV-associated tumors in Rag2−/−γc−/− and humanized mice. Because expanding Vδ2-T cells and preparing autologous Vδ2-T-Exos from cancer patients ex vivo in large scale is challenging, we explored the antitumor activity of allogeneic Vδ2-T-Exos in humanized mouse cancer models. Here, we found that allogeneic Vδ2-T-Exos had more effective antitumor activity than autologous Vδ2-T-Exos in humanized mice; the allogeneic Vδ2-T-Exos increased the infiltration of T cells into tumor tissues and induced more robust CD4 and CD8 T cell–mediated antitumor immunity. Compared with exosomes derived from NK cells (NK-Exos) with direct cytotoxic antitumor activity or dendritic cells (DC-Exos) that induced T cell antitumor responses, Vδ2-T-Exos directly killed tumor cells and induced T cell–mediated antitumor response, thus resulting in more effective control of EBV-associated tumors. This study provided proof of concept for the strategy of using Vδ2-T-Exos, especially allogeneic Vδ2-T-Exos, to treat EBV-associated tumors.-
dc.languageeng-
dc.publisherAmerican Association for the Advancement of Science. The Journal's web site is located at http://www.sciencemag.org/marketing/stm/-
dc.relation.ispartofScience Translational Medicine-
dc.rightsScience Translational Medicine. Copyright © American Association for the Advancement of Science.-
dc.rightsThis is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in [Science Journal Title] on [Volume number and date], DOI: [insert DOI number].-
dc.titleExosomes derived from Vδ2-T cells control Epstein-Barr virus-associated tumors and induce T cell antitumor immunity-
dc.typeArticle-
dc.identifier.emailWang, X: xweiwang@connect.hku.hk-
dc.identifier.emailPei, Y: peiyujun@HKUCC-COM.hku.hk-
dc.identifier.emailWang, X: wxia0951@hku.hk-
dc.identifier.emailWong, WHS: whswong@hku.hk-
dc.identifier.emailNg, IOL: iolng@hku.hk-
dc.identifier.emailLee, PPW: ppwlee@hku.hk-
dc.identifier.emailChan, GCF: gcfchan@hku.hk-
dc.identifier.emailLau, YL: lauylung@hku.hk-
dc.identifier.emailTu, W: wwtu@hku.hk-
dc.identifier.authorityNg, IOL=rp00335-
dc.identifier.authorityLee, PPW=rp00462-
dc.identifier.authorityChan, GCF=rp00431-
dc.identifier.authorityLau, YL=rp00361-
dc.identifier.authorityTu, W=rp00416-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1126/scitranslmed.aaz3426-
dc.identifier.pmid32998970-
dc.identifier.scopuseid_2-s2.0-85092494877-
dc.identifier.hkuros314826-
dc.identifier.volume12-
dc.identifier.issue563-
dc.identifier.spagearticle no. eaaz3426-
dc.identifier.epagearticle no. eaaz3426-
dc.identifier.isiWOS:000573722200004-
dc.publisher.placeUnited States-
dc.identifier.issnl1946-6234-

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