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dc.contributor.authorBak, S. Peter G.
dc.contributor.authorBarnkob, Mike Stein
dc.contributor.authorWittrup, Karl Dane
dc.contributor.authorChen, Jianzhu
dc.date.accessioned2014-11-17T20:09:53Z
dc.date.available2014-11-17T20:09:53Z
dc.date.issued2013-09
dc.date.submitted2013-09
dc.identifier.issn2326-6066
dc.identifier.issn2326-6074
dc.identifier.urihttp://hdl.handle.net/1721.1/91603
dc.description.abstractStimulation of patients' immune systems for the treatment of solid tumors is an emerging therapeutic paradigm. The use of enriched autologous T cells for adoptive cell therapy or vaccination with antigen-loaded dendritic cells have shown clinical efficacy in melanoma and prostate cancer, respectively. However, the long-term effects of immune responses on selection and outgrowth of antigen-negative tumor cells in specific tumor types must be determined to understand and achieve long-term therapeutic effects. In this study, we have investigated the expression of a tumor-specific antigen in situ after treatment with tumor-specific CD8[superscript +] T cells in an autochthonous mouse model of prostate cancer. After T-cell treatment, aggregates of dead antigen-positive tumor cells were concentrated in the lumen of the prostate gland and were eventually eliminated from the prostate tissue. Despite the elimination of antigen-positive tumor cells, prostate tumor continued to grow in T-cell–treated mice. Interestingly, the remaining tumor cells were antigen negative and downregulated MHC class I expression. These results show that CD8[superscript +] T cells are effective in eliminating antigen-bearing prostate tumor cells but they also can select for the outgrowth of antigen-negative tumor cells. These findings provide insights into the requirements for an effective cancer immunotherapy within the prostate that not only induces potent immune responses but also avoids selection and outgrowth of antigen-negative tumor cells.en_US
dc.description.sponsorshipAmerican Cancer Society (Postdoctoral Fellowship 12109-PF-11-025-01-LIB)en_US
dc.description.sponsorshipJohn D. Proctor Foundation (Margaret A. Cunningham Immune Mechanisms in Cancer Research Fellowship)en_US
dc.description.sponsorshipUnited States. Army Medical Research and Materiel Command (Prostate Cancer Research Program Grant)en_US
dc.description.sponsorshipNational Cancer Institute (U.S.) (Koch Institute Support (Core) Grant P30-CA14051)en_US
dc.language.isoen_US
dc.publisherAmerican Association for Cancer Researchen_US
dc.relation.isversionofhttp://dx.doi.org/10.1158/2326-6066.cir-13-0109en_US
dc.rightsCreative Commons Attribution-Noncommercial-Share Alikeen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/en_US
dc.sourcePMCen_US
dc.titleCD8[superscript +] T-cell Responses Rapidly Select for Antigen-Negative Tumor Cells in the Prostateen_US
dc.typeArticleen_US
dc.identifier.citationBak, S. P., M. S. Barnkob, K. D. Wittrup, and J. Chen. “CD8+ T-Cell Responses Rapidly Select for Antigen-Negative Tumor Cells in the Prostate.” Cancer Immunology Research 1, no. 6 (December 1, 2013): 393–401.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineeringen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemical Engineeringen_US
dc.contributor.departmentKoch Institute for Integrative Cancer Research at MITen_US
dc.contributor.mitauthorBak, S. Peter G.en_US
dc.contributor.mitauthorBarnkob, Mike Steinen_US
dc.contributor.mitauthorWittrup, Karl Daneen_US
dc.contributor.mitauthorChen, Jianzhuen_US
dc.relation.journalCancer Immunology Researchen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsBak, S. P.; Barnkob, M. S.; Wittrup, K. D.; Chen, J.en_US
dc.identifier.orcidhttps://orcid.org/0000-0003-2398-5896
dc.identifier.orcidhttps://orcid.org/0000-0002-5687-6154
dspace.mitauthor.errortrue
mit.licenseOPEN_ACCESS_POLICYen_US
mit.metadata.statusComplete


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