File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Conference Paper: TLR4 induced PD-1 expression on myeloid dendritic cells promotes post-transplant HCC recurrence

TitleTLR4 induced PD-1 expression on myeloid dendritic cells promotes post-transplant HCC recurrence
Authors
Issue Date2021
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.transplantjournal.com
Citation
2021 Virtual International Congress of ILTS, ELITA and LICAGE, 5-8 May 2021. In Transplantation, 2021, v. 105 n. 8S, p. 4 How to Cite?
AbstractBackground: Immature and paralyzed dendritic cells (DCs) in the tumor microenvironment impede antitumor immunity. PD-1 is known to be not only expressed on T and B lymphocytes but also expressed on myeloid cells such as macrophages and DCs. Recent evidence demonstrates that TLR4 mediates PD-1 expression on DCs, and PD-1+ DCs significantly suppress CD8+ T cell function and antitumor immunity. In this study, we aim to investigate the role of PD-1+ dendritic cells on tumor recurrence after LT. Methods: The expression of PD-1 on DCs was analyzed both in clinical samples and rat orthotopic liver transplantation model. The mechanism of TLR4 on DCs was explored in human monocyte-derived DCs (Mo-DCs) and TLR-4-/- mice. The role of TLR4 signaling on tumor progression was further investigated in mouse orthotopic liver tumor model. Results: Clinically, PD-1 expression was upregulated in CD11c+ myeloid DCs (mDCs) (Fig. 1A), but not in plasmacytoid DCs (pDCs) in liver graft. PD-1 expression on mDCs was also elevated in rats with orthotopic LT (Fig 1B). Recipients with HCC recurrence had higher level of PD-1 expression on CD11c+ cells (Fig 2A). The intragraft mRNA expression of PD-1 was significantly up-regulated and positively correlated with TLR4 after LT (Fig 2B). Functionally, LPS promoted the expression of PD-1, IL-10, TGF-β and MHCII in Mo-DCs. LPS also promoted apoptosis in Mo-DCs (Fig 3A). The PD-1 expression on mDCs was significantly decreased after hepatic I/R injury in TLR4-/- mice (Fig 3B). TLR4 antagonist increased the number of mDCs and suppressed HCC growth in mice after hepatic I/R injury with major hepatectomy (Fig 4). Conclusion: The acute phase graft injury promoted PD-1 expression on DCs via TLR4 signaling, and PD-1+ DCs promoted HCC recurrence after LT.
DescriptionOral presentations - Rising Star Symposium, Track 1 - Rising Star Plenary Session - abstract no. O-003
Persistent Identifierhttp://hdl.handle.net/10722/308216
ISSN
2023 Impact Factor: 5.3
2023 SCImago Journal Rankings: 1.371

 

DC FieldValueLanguage
dc.contributor.authorPang, L-
dc.contributor.authorNg, KTP-
dc.contributor.authorZhu, J-
dc.contributor.authorLiu, H-
dc.contributor.authorYeung, OWH-
dc.contributor.authorChen, ZW-
dc.contributor.authorMan, K-
dc.date.accessioned2021-11-12T13:44:07Z-
dc.date.available2021-11-12T13:44:07Z-
dc.date.issued2021-
dc.identifier.citation2021 Virtual International Congress of ILTS, ELITA and LICAGE, 5-8 May 2021. In Transplantation, 2021, v. 105 n. 8S, p. 4-
dc.identifier.issn0041-1337-
dc.identifier.urihttp://hdl.handle.net/10722/308216-
dc.descriptionOral presentations - Rising Star Symposium, Track 1 - Rising Star Plenary Session - abstract no. O-003-
dc.description.abstractBackground: Immature and paralyzed dendritic cells (DCs) in the tumor microenvironment impede antitumor immunity. PD-1 is known to be not only expressed on T and B lymphocytes but also expressed on myeloid cells such as macrophages and DCs. Recent evidence demonstrates that TLR4 mediates PD-1 expression on DCs, and PD-1+ DCs significantly suppress CD8+ T cell function and antitumor immunity. In this study, we aim to investigate the role of PD-1+ dendritic cells on tumor recurrence after LT. Methods: The expression of PD-1 on DCs was analyzed both in clinical samples and rat orthotopic liver transplantation model. The mechanism of TLR4 on DCs was explored in human monocyte-derived DCs (Mo-DCs) and TLR-4-/- mice. The role of TLR4 signaling on tumor progression was further investigated in mouse orthotopic liver tumor model. Results: Clinically, PD-1 expression was upregulated in CD11c+ myeloid DCs (mDCs) (Fig. 1A), but not in plasmacytoid DCs (pDCs) in liver graft. PD-1 expression on mDCs was also elevated in rats with orthotopic LT (Fig 1B). Recipients with HCC recurrence had higher level of PD-1 expression on CD11c+ cells (Fig 2A). The intragraft mRNA expression of PD-1 was significantly up-regulated and positively correlated with TLR4 after LT (Fig 2B). Functionally, LPS promoted the expression of PD-1, IL-10, TGF-β and MHCII in Mo-DCs. LPS also promoted apoptosis in Mo-DCs (Fig 3A). The PD-1 expression on mDCs was significantly decreased after hepatic I/R injury in TLR4-/- mice (Fig 3B). TLR4 antagonist increased the number of mDCs and suppressed HCC growth in mice after hepatic I/R injury with major hepatectomy (Fig 4). Conclusion: The acute phase graft injury promoted PD-1 expression on DCs via TLR4 signaling, and PD-1+ DCs promoted HCC recurrence after LT.-
dc.languageeng-
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.transplantjournal.com-
dc.relation.ispartofTransplantation-
dc.relation.ispartof2021 Virtual International Congress of ILTS, ELITA & LICAGE-
dc.titleTLR4 induced PD-1 expression on myeloid dendritic cells promotes post-transplant HCC recurrence-
dc.typeConference_Paper-
dc.identifier.emailPang, L: leepang@connect.hku.hk-
dc.identifier.emailNg, KTP: ledodes@hku.hk-
dc.identifier.emailYeung, OWH: why21@hku.hk-
dc.identifier.emailChen, ZW: zchenai@hku.hk-
dc.identifier.emailMan, K: kwanman@hku.hk-
dc.identifier.authorityNg, KTP=rp01720-
dc.identifier.authorityChen, ZW=rp00243-
dc.identifier.authorityMan, K=rp00417-
dc.description.natureabstract-
dc.identifier.hkuros330002-
dc.identifier.volume105-
dc.identifier.issue8S-
dc.identifier.spage4-
dc.identifier.epage4-
dc.publisher.placeUnited States-
dc.identifier.partofdoi10.1097/01.tp.0000789500.50801.c7-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats