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- Publisher Website: 10.1080/2162402X.2018.1518672
- Scopus: eid_2-s2.0-85055125548
- PMID: 30546960
- WOS: WOS:000457342800024
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Article: Virotherapy-recruited PMN-MDSC infiltration of mesothelioma blocks antitumor CTL by IL-10-mediated dendritic cell suppression
Title | Virotherapy-recruited PMN-MDSC infiltration of mesothelioma blocks antitumor CTL by IL-10-mediated dendritic cell suppression |
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Authors | |
Keywords | CTLs MDSCs Mesothelioma Modified vaccinia Tiantan Virotherapy |
Issue Date | 2019 |
Publisher | Taylor & 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? |
Abstract | Antitumor 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 Identifier | http://hdl.handle.net/10722/272002 |
ISSN | 2023 Impact Factor: 6.5 2023 SCImago Journal Rankings: 2.345 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Tan, Z | - |
dc.contributor.author | Liu, L | - |
dc.contributor.author | Chiu, MS | - |
dc.contributor.author | Cheung, KW | - |
dc.contributor.author | Yan, CW | - |
dc.contributor.author | Yu, Z | - |
dc.contributor.author | Lee, BK | - |
dc.contributor.author | Liu, W | - |
dc.contributor.author | Man, K | - |
dc.contributor.author | Chen, Z | - |
dc.date.accessioned | 2019-07-20T10:33:47Z | - |
dc.date.available | 2019-07-20T10:33:47Z | - |
dc.date.issued | 2019 | - |
dc.identifier.citation | OncoImmunology, 2019, v. 8 n. 1, article no. e1518672 | - |
dc.identifier.issn | 2162-402X | - |
dc.identifier.uri | http://hdl.handle.net/10722/272002 | - |
dc.description.abstract | Antitumor 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.language | eng | - |
dc.publisher | Taylor & Francis Inc. The Journal's web site is located at http://www.tandfonline.com/koni | - |
dc.relation.ispartof | OncoImmunology | - |
dc.subject | CTLs | - |
dc.subject | MDSCs | - |
dc.subject | Mesothelioma | - |
dc.subject | Modified vaccinia Tiantan | - |
dc.subject | Virotherapy | - |
dc.title | Virotherapy-recruited PMN-MDSC infiltration of mesothelioma blocks antitumor CTL by IL-10-mediated dendritic cell suppression | - |
dc.type | Article | - |
dc.identifier.email | Tan, Z: zwtan@hku.hk | - |
dc.identifier.email | Liu, L: liuli71@hkucc.hku.hk | - |
dc.identifier.email | Chiu, MS: carolcms@hku.hk | - |
dc.identifier.email | Man, K: kwanman@hku.hk | - |
dc.identifier.email | Chen, Z: zchenai@hku.hk | - |
dc.identifier.authority | Liu, L=rp00268 | - |
dc.identifier.authority | Man, K=rp00417 | - |
dc.identifier.authority | Chen, Z=rp00243 | - |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.doi | 10.1080/2162402X.2018.1518672 | - |
dc.identifier.pmid | 30546960 | - |
dc.identifier.pmcid | PMC6287797 | - |
dc.identifier.scopus | eid_2-s2.0-85055125548 | - |
dc.identifier.hkuros | 298379 | - |
dc.identifier.volume | 8 | - |
dc.identifier.issue | 1 | - |
dc.identifier.spage | article no. e1518672 | - |
dc.identifier.epage | article no. e1518672 | - |
dc.identifier.isi | WOS:000457342800024 | - |
dc.publisher.place | United States | - |
dc.identifier.issnl | 2162-4011 | - |