Oncolytic adenovirus coexpressing interleukin-12 and decorin overcomes Treg-mediated immunosuppression inducing potent antitumor effects in a weakly immunogenic tumor model

DSpace/Manakin Repository

Oncolytic adenovirus coexpressing interleukin-12 and decorin overcomes Treg-mediated immunosuppression inducing potent antitumor effects in a weakly immunogenic tumor model

Show simple item record

dc.contributor.author Oh, Eonju en_US
dc.contributor.author Choi, Il-Kyu en_US
dc.contributor.author Hong, JinWoo en_US
dc.contributor.author Yun, Chae-Ok en_US
dc.date.accessioned 2017-05-01T19:27:42Z
dc.date.issued 2017 en_US
dc.identifier.citation Oh, Eonju, Il-Kyu Choi, JinWoo Hong, and Chae-Ok Yun. 2017. “Oncolytic adenovirus coexpressing interleukin-12 and decorin overcomes Treg-mediated immunosuppression inducing potent antitumor effects in a weakly immunogenic tumor model.” Oncotarget 8 (3): 4730-4746. doi:10.18632/oncotarget.13972. http://dx.doi.org/10.18632/oncotarget.13972. en
dc.identifier.issn en
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:32630622
dc.description.abstract Interleukin (IL)-12 is a potent antitumor cytokine. However, immunosuppressive tumor microenvironments containing transforming growth factor-β (TGF-β) attenuate cytokine-mediated antitumor immune responses. To enhance the efficacy of IL-12-mediated cancer immunotherapy, decorin (DCN) was explored as an adjuvant for overcoming TGF-β-mediated immunosuppression. We designed and generated a novel oncolytic adenovirus (Ad) coexpressing IL-12 and DCN (RdB/IL12/DCN). RdB/IL12/DCN-treated tumors showed significantly greater levels of interferon (IFN)-γ, tumor necrosis factor-α, monocyte chemoattractant protein-1, and IFN-γ-secreting immune cells than tumors treated with cognate control oncolytic Ad expressing a single therapeutic gene (RdB/DCN or RdB/IL12). Moreover, RdB/IL12/DCN attenuated intratumoral TGF-β expression, which positively correlated with reduction of Treg cells in draining lymph nodes and tumor tissues. Furthermore, tumor tissue treated with RdB/IL12/DCN showed increases infiltration of CD8+ T cells and proficient viral spreading within tumor tissues. These results demonstrated that an oncolytic Ad co-expressing IL-12 and DCN induces a potent antitumor immune response via restoration of antitumor immune function in a weakly immunogenic murine 4T1 orthotopic breast cancer model. These findings provide new insights into the therapeutic mechanisms of IL-12 plus DCN, making it a promising cancer immunotherapeutic agent for overcoming tumor-induced immunosuppression. en
dc.language.iso en_US en
dc.publisher Impact Journals LLC en
dc.relation.isversionof doi:10.18632/oncotarget.13972 en
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5354867/pdf/ en
dash.license LAA en_US
dc.subject oncolytic adenovirus en
dc.subject IL-12 en
dc.subject decorin en
dc.subject TGF-β en
dc.subject Treg en
dc.title Oncolytic adenovirus coexpressing interleukin-12 and decorin overcomes Treg-mediated immunosuppression inducing potent antitumor effects in a weakly immunogenic tumor model en
dc.type Journal Article en_US
dc.description.version Version of Record en
dc.relation.journal Oncotarget en
dash.depositing.author Choi, Il-Kyu en_US
dc.date.available 2017-05-01T19:27:42Z

Files in this item

Files Size Format View
5354867.pdf 9.791Mb PDF View/Open

This item appears in the following Collection(s)

Show simple item record

 
 

Search DASH


Advanced Search
 
 

Submitters