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Article: Virotherapy-recruited PMN-MDSC infiltration of mesothelioma blocks antitumor CTL by IL-10-mediated dendritic cell suppression

TitleVirotherapy-recruited PMN-MDSC infiltration of mesothelioma blocks antitumor CTL by IL-10-mediated dendritic cell suppression
Authors
KeywordsCTLs
MDSCs
Mesothelioma
Modified vaccinia Tiantan
Virotherapy
Issue Date2019
PublisherTaylor & Francis Inc. The Journal's web site is located at http://www.tandfonline.com/koni
Citation
OncoImmunology, 2019, v. 8 n. 1, article no. e1518672 How to Cite?
AbstractAntitumor cytotoxic T lymphocytes (CTLs) are essential for immune surveillance, yet the blockade of eliciting such CTLs during oncolytic virotherapy remains incompletely understood. Here, we show that oncolysis of mesothelioma by modified vaccinia Tiantan (MVTT) induces damage-associated molecular patterns exposure. Although MVTT leads to regression of established mesothelioma dose-dependently, antitumor CTLs are rarely induced. Mechanistically, MVTT virotherapy generates C-X-C chemokines that recruit CXCR2-expressing polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) into tumor microenvironment, where they suppress dendritic cells (DCs) by producing IL-10 and halt CTL responses. During the virotherapy, however, depletion of PMN-MDSCs but not of monocytic (M)-MDSCs results in the induction of potent antitumor CTLs that not only eradicate established mesothelioma but also prevent the second tumor challenge. Our findings suggest that vaccinia virotherapy may combine strategies that prevent the chemotactic recruitment of PMN-MDSCs, block their suppression on DCs or deplete PMN-MDSCs in order to induce potent CTLs for tumor eradication.
Persistent Identifierhttp://hdl.handle.net/10722/272002
ISSN
2017 Impact Factor: 5.503
2015 SCImago Journal Rankings: 1.485
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorTan, Z-
dc.contributor.authorLiu, L-
dc.contributor.authorChiu, MS-
dc.contributor.authorCheung, KW-
dc.contributor.authorYan, CW-
dc.contributor.authorYu, Z-
dc.contributor.authorLee, BK-
dc.contributor.authorLiu, W-
dc.contributor.authorMan, K-
dc.contributor.authorChen, Z-
dc.date.accessioned2019-07-20T10:33:47Z-
dc.date.available2019-07-20T10:33:47Z-
dc.date.issued2019-
dc.identifier.citationOncoImmunology, 2019, v. 8 n. 1, article no. e1518672-
dc.identifier.issn2162-402X-
dc.identifier.urihttp://hdl.handle.net/10722/272002-
dc.description.abstractAntitumor cytotoxic T lymphocytes (CTLs) are essential for immune surveillance, yet the blockade of eliciting such CTLs during oncolytic virotherapy remains incompletely understood. Here, we show that oncolysis of mesothelioma by modified vaccinia Tiantan (MVTT) induces damage-associated molecular patterns exposure. Although MVTT leads to regression of established mesothelioma dose-dependently, antitumor CTLs are rarely induced. Mechanistically, MVTT virotherapy generates C-X-C chemokines that recruit CXCR2-expressing polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) into tumor microenvironment, where they suppress dendritic cells (DCs) by producing IL-10 and halt CTL responses. During the virotherapy, however, depletion of PMN-MDSCs but not of monocytic (M)-MDSCs results in the induction of potent antitumor CTLs that not only eradicate established mesothelioma but also prevent the second tumor challenge. Our findings suggest that vaccinia virotherapy may combine strategies that prevent the chemotactic recruitment of PMN-MDSCs, block their suppression on DCs or deplete PMN-MDSCs in order to induce potent CTLs for tumor eradication.-
dc.languageeng-
dc.publisherTaylor & Francis Inc. The Journal's web site is located at http://www.tandfonline.com/koni-
dc.relation.ispartofOncoImmunology-
dc.subjectCTLs-
dc.subjectMDSCs-
dc.subjectMesothelioma-
dc.subjectModified vaccinia Tiantan-
dc.subjectVirotherapy-
dc.titleVirotherapy-recruited PMN-MDSC infiltration of mesothelioma blocks antitumor CTL by IL-10-mediated dendritic cell suppression-
dc.typeArticle-
dc.identifier.emailTan, Z: zwtan@hku.hk-
dc.identifier.emailLiu, L: liuli71@hkucc.hku.hk-
dc.identifier.emailChiu, MS: carolcms@hku.hk-
dc.identifier.emailMan, K: kwanman@hku.hk-
dc.identifier.emailChen, Z: zchenai@hku.hk-
dc.identifier.authorityLiu, L=rp00268-
dc.identifier.authorityMan, K=rp00417-
dc.identifier.authorityChen, Z=rp00243-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1080/2162402X.2018.1518672-
dc.identifier.pmid30546960-
dc.identifier.pmcidPMC6287797-
dc.identifier.scopuseid_2-s2.0-85055125548-
dc.identifier.hkuros298379-
dc.identifier.volume8-
dc.identifier.issue1-
dc.identifier.spagearticle no. e1518672-
dc.identifier.epagearticle no. e1518672-
dc.identifier.isiWOS:000457342800024-
dc.publisher.placeUnited States-

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