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dc.contributor.authorAli, Omar Abdel-Rahman
dc.contributor.authorEmerich, Dwaine
dc.contributor.authorDranoff, Glenn
dc.contributor.authorMooney, David J.
dc.date.accessioned2015-06-09T17:53:03Z
dc.date.issued2009
dc.identifier.citationAli, O. A., D. Emerich, G. Dranoff, and D. J. Mooney. 2009. “In Situ Regulation of DC Subsets and T Cells Mediates Tumor Regression in Mice.” Science Translational Medicine 1 (8) (November 25): 8ra19–8ra19. doi:10.1126/scitranslmed.3000359.en_US
dc.identifier.issn1946-6234en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:16235677
dc.description.abstractVaccines are largely ineffective for patients with established cancer, as advanced disease requires potent and sustained activation of CD8\(^+\) cytotoxic T lymphocytes (CTLs) to kill tumor cells and clear the disease. Recent studies have found that subsets of dendritic cells (DCs) specialize in antigen cross-presentation and in the production of cytokines, which regulate both CTLs and T regulatory (Treg) cells that shut down effector T cell responses. Here, we addressed the hypothesis that coordinated regulation of a DC network, and plasmacytoid DCs (pDCs) and CD8\(^+\) DCs in particular, could enhance host immunity in mice. We used functionalized biomaterials incorporating various combinations of an inflammatory cytokine, immune danger signal, and tumor lysates to control the activation and localization of host DC populations in situ. The numbers of pDCs and CD8\(^+\) DCs, and the endogenous production of interleukin-12, all correlated strongly with the magnitude of protective antitumor immunity and the generation of potent CD8\(^+\) CTLs. Vaccination by this method maintained local and systemic CTL responses for extended periods while inhibiting FoxP3 Treg activity during antigen clearance, resulting in complete regression of distant and established melanoma tumors. The efficacy of this vaccine as a monotherapy against large invasive tumors may be a result of the local activity of pDCs and CD8\(^+\) DCs induced by persistent danger and antigen signaling at the vaccine site. These results indicate that a critical pattern of DC subsets correlates with the evolution of therapeutic antitumor responses and provide a template for future vaccine design.en_US
dc.description.sponsorshipEngineering and Applied Sciencesen_US
dc.description.sponsorshipOther Research Uniten_US
dc.language.isoen_USen_US
dc.publisherAmerican Association for the Advancement of Science (AAAS)en_US
dc.relation.isversionofdoi:10.1126/scitranslmed.3000359en_US
dash.licenseLAA
dc.titleIn Situ Regulation of DC Subsets and T Cells Mediates Tumor Regression in Miceen_US
dc.typeJournal Articleen_US
dc.description.versionAccepted Manuscripten_US
dc.relation.journalScience Translational Medicineen_US
dash.depositing.authorMooney, David J.
dash.waiver2009-11-02
dc.date.available2015-06-09T17:53:03Z
dash.affiliation.otherHarvard Medical Schoolen_US
dc.identifier.doi10.1126/scitranslmed.3000359*
dash.contributor.affiliatedAli, Omar Abdel-Rahman
dash.contributor.affiliatedDranoff, Glenn
dash.contributor.affiliatedMooney, David


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