Agonistic anti-4-1BB mAb promotes the maturation and activation of hypoxic dendritic cells

Abstract

Event Abstract Back to Event Agonistic anti-4-1BB mAb promotes the maturation and activation of hypoxic dendritic cells Qun WANG1*, Chunmei LIU1, Zhaojing DONG1, Chun GUO1 and Lining ZHANG1 1 Shandong University School of Medicine, China Hypoxia resident in solid tumor and inflammatory tissues links closely with immune function. Maturation and activation of dendritic cells (DCs) are essential to drive immune response in hypoxic microenvironments. 4-1BB has been implicated involved in regulation of DC function, but its effects on hypoxic DCs remain unclear. In this study, we stimulated 4-1BB on murine hypoxic DCs using agonistic anti-4-1BB mAb and examined the phenotypic and functional changes of these DCs. We showed hypoxia had little influence on differentiation of DCs, but suppressed their maturation and activation via down-regulation of pro-inflammatory cytokines, MHC class II and co-stimulatory molecules. Compared with normoxic DCs, hypoxic DCs showed a slightly decreased expression of 4-1BB. Treatment of hypoxic DCs with anti-4-1BB mAb dramatically up-regulated the expression of pro-inflammatory cytokines including IL-6, IL-12 and TNF-α; the expression of matrix metalloproteinase 9 related to migration also increased in these DCs. Although anti-4-1BB mAb moderately up-regulated co-stimulatory molecules CD80, CD86 and MHC class II molecules on hypoxic DCs (remain lower compared to normoxic DCs), these DCs still showed limited ability to stimulate allogeneic CD4+T cell proliferation compared with normoxic DCs. All together, we demonstrate that anti-4-1BB mAb partially restores the maturation and activation of hypoxic DCs by promoting their phenotypic maturation, inflammatory cytokines production and migration ability, thereby enhancing the immune function of DCs in hypoxic microenvironments. Acknowledgements This work was supported by the National Natural Science Foundation of China (81270923, 30700729), Shangdong Young Scientists Award Fund (2011BSE27110). Keywords: hypoxia, 4-1BB, mAb, dendritic cell, maturation Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Innate immunity Citation: WANG Q, LIU C, DONG Z, GUO C and ZHANG L (2013). Agonistic anti-4-1BB mAb promotes the maturation and activation of hypoxic dendritic cells. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00798 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 17 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Qun WANG, Shandong University School of Medicine, Jinan, 250012, China, wangqun@sdu.edu.cn Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Qun WANG Chunmei LIU Zhaojing DONG Chun GUO Lining ZHANG Google Qun WANG Chunmei LIU Zhaojing DONG Chun GUO Lining ZHANG Google Scholar Qun WANG Chunmei LIU Zhaojing DONG Chun GUO Lining ZHANG PubMed Qun WANG Chunmei LIU Zhaojing DONG Chun GUO Lining ZHANG Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.