dc.contributor.author | Szeto, Gregory L. | |
dc.contributor.author | Overwijk, Willem W. | |
dc.contributor.author | Tzeng, Alice | |
dc.contributor.author | Kauke, Monique Jacqueline | |
dc.contributor.author | Zhu, Eric Franklin | |
dc.contributor.author | Moynihan, Kelly Dare | |
dc.contributor.author | Opel, Cary Francis | |
dc.contributor.author | Yang, Nicole Jie Yeon | |
dc.contributor.author | Mehta, Naveen | |
dc.contributor.author | Irvine, Darrell J | |
dc.contributor.author | Wittrup, Karl Dane | |
dc.date.accessioned | 2017-03-17T15:44:07Z | |
dc.date.available | 2017-03-17T15:44:07Z | |
dc.date.issued | 2016-12 | |
dc.date.submitted | 2016-09 | |
dc.identifier.issn | 22111247 | |
dc.identifier.issn | 2211-1247 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/107465 | |
dc.description.abstract | Numerous synergistic cancer immunotherapy combinations have been identified, but the effects of relative dose timing are rarely considered. In established syngeneic mouse tumor models, we found that staggering interferon-α (IFNα) administration after, rather than before or simultaneously with, serum-persistent interleukin-2 (IL-2) and tumor-specific antibody significantly increased long-term survival. Successful combination therapy required IFNα-induced activation of cross-presenting CD8α[superscript +] dendritic cells (DCs) following the release of antigenic tumor debris by the IL-2- and antibody-mediated immune response. Due to decreased phagocytic ability post-maturation, DCs activated too early captured less antigen and could not effectively prime CD8[superscript +] T cells. Temporally programming DC activation to occur after tumoricidal activity enhanced tumor control by multiple distinct combination immunotherapies, highlighting dose schedule as an underappreciated factor that can profoundly affect the success of multi-component immunotherapies. | en_US |
dc.description.sponsorship | National Cancer Institute (U.S.) (Grants NCI CA174795 and CA101830) | en_US |
dc.description.sponsorship | Ludwig Center for Molecular Oncology at MIT (Graduate Fellowship) | en_US |
dc.description.sponsorship | Thomas and Stacey Siebel Foundation (Scholarship) | en_US |
dc.description.sponsorship | National Science Foundation (U.S.). Graduate Research Fellowship Program | en_US |
dc.description.sponsorship | Hertz Foundation (Fellowship) | en_US |
dc.language.iso | en_US | |
dc.publisher | Elsevier | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1016/j.celrep.2016.11.020 | en_US |
dc.rights | Creative Commons Attribution-NonCommercial-NoDerivs License | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | en_US |
dc.source | Elsevier | en_US |
dc.title | Temporally Programmed CD8α[superscrip +] DC Activation Enhances Combination Cancer Immunotherapy | en_US |
dc.title.alternative | Temporally Programmed CD8α+ DC Activation Enhances Combination Cancer Immunotherapy | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Tzeng, Alice et al. “Temporally Programmed CD8α+ DC Activation Enhances Combination Cancer Immunotherapy.” Cell Reports 17.10 (2016): 2503–2511. | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biological Engineering | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Chemical Engineering | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Materials Science and Engineering | en_US |
dc.contributor.department | Koch Institute for Integrative Cancer Research at MIT | en_US |
dc.contributor.mitauthor | Tzeng, Alice | |
dc.contributor.mitauthor | Kauke, Monique Jacqueline | |
dc.contributor.mitauthor | Zhu, Eric Franklin | |
dc.contributor.mitauthor | Moynihan, Kelly Dare | |
dc.contributor.mitauthor | Opel, Cary Francis | |
dc.contributor.mitauthor | Yang, Nicole Jie Yeon | |
dc.contributor.mitauthor | Mehta, Naveen | |
dc.contributor.mitauthor | Irvine, Darrell J | |
dc.contributor.mitauthor | Wittrup, Karl Dane | |
dc.relation.journal | Cell Reports | en_US |
dc.eprint.version | Final published version | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dspace.orderedauthors | Tzeng, Alice; Kauke, Monique J.; Zhu, Eric F.; Moynihan, Kelly D.; Opel, Cary F.; Yang, Nicole J.; Mehta, Naveen; Kelly, Ryan L.; Szeto, Gregory L.; Overwijk, Willem W.; Irvine, Darrell J.; Wittrup, K. Dane | en_US |
dspace.embargo.terms | N | en_US |
dc.identifier.orcid | https://orcid.org/0000-0001-7316-6923 | |
dc.identifier.orcid | https://orcid.org/0000-0002-0013-3941 | |
dc.identifier.orcid | https://orcid.org/0000-0003-3789-1516 | |
dc.identifier.orcid | https://orcid.org/0000-0002-0882-7761 | |
dc.identifier.orcid | https://orcid.org/0000-0003-3480-6750 | |
dc.identifier.orcid | https://orcid.org/0000-0003-2398-5896 | |
mit.license | PUBLISHER_CC | en_US |
mit.metadata.status | Complete | |