Elimination of Metastatic Melanoma Using Gold Nanoshell-Enabled Photothermal Therapy and Adoptive T Cell Transfer

dc.citation.firstpagee69073en_US
dc.citation.issueNumber7en_US
dc.citation.journalTitlePLoS Oneen_US
dc.citation.volumeNumber8en_US
dc.contributor.authorBear, Adham S.en_US
dc.contributor.authorKennedy, Laura C.en_US
dc.contributor.authorYoung, Joseph K.en_US
dc.contributor.authorPerna, Serena K.en_US
dc.contributor.authorAlmeida, Joao Paulo Mattosen_US
dc.contributor.authorLin, Adam Y.en_US
dc.contributor.authorEckels, Phillip C.en_US
dc.contributor.authorDrezek, Rebekah A.en_US
dc.contributor.authorFoster, Aaron E.en_US
dc.date.accessioned2013-08-02T15:52:41Zen_US
dc.date.available2013-08-02T15:52:41Zen_US
dc.date.issued2013en_US
dc.description.abstractAblative treatments such as photothermal therapy (PTT) are attractive anticancer strategies because they debulk accessible tumor sites while simultaneously priming antitumor immune responses. However, the immune response following thermal ablation is often insufficient to treat metastatic disease. Here we demonstrate that PTT induces the expression of proinflammatory cytokines and chemokines and promotes the maturation of dendritic cells within tumor-draining lymph nodes, thereby priming antitumor T cell responses. Unexpectedly, however, these immunomodulatory effects were not beneficial to overall antitumor immunity. We found that PTT promoted the infiltration of secondary tumor sites by CD11b+Ly-6G/C+ myeloid-derived suppressor cells, consequently failing to slow the growth of poorly immunogenic B16-F10 tumors and enhancing the growth of distant lung metastases. To exploit the beneficial effects of PTT activity against local tumors and on antitumor immunity whilst avoiding the adverse consequences, we adoptively transferred gp100-specific pmel T cells following PTT. The combination of local control by PTT and systemic antitumor immune reactivity provided by adoptively transferred T cells prevented primary tumor recurrence post-ablation, inhibited tumor growth at distant sites, and abrogated the outgrowth of lung metastases. Hence, the combination of PTT and systemic immunotherapy prevented the adverse effects of PTT on metastatic tumor growth and optimized overall tumor control.en_US
dc.embargo.termsnoneen_US
dc.identifier.citationBear, Adham S., Kennedy, Laura C., Young, Joseph K., et al.. "Elimination of Metastatic Melanoma Using Gold Nanoshell-Enabled Photothermal Therapy and Adoptive T Cell Transfer." <i>PLoS One,</i> 8, no. 7 (2013) Public Library of Science: e69073. http://dx.doi.org/10.1371/journal.pone.0069073.en_US
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pone.0069073en_US
dc.identifier.urihttps://hdl.handle.net/1911/71719en_US
dc.language.isoengen_US
dc.publisherPublic Library of Scienceen_US
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.titleElimination of Metastatic Melanoma Using Gold Nanoshell-Enabled Photothermal Therapy and Adoptive T Cell Transferen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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