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dc.contributor.authorA. Antony, Paulen_US
dc.contributor.authorA. Quezada, Sergioen_US
dc.contributor.authorBlasberg, Ronalden_US
dc.contributor.authorFan, Xiaozhouen_US
dc.contributor.authorMerghoub, Tahaen_US
dc.contributor.authorMuranski, Pawelen_US
dc.contributor.authorP. Allison, Jamesen_US
dc.contributor.authorP. Restifo, Nicholasen_US
dc.contributor.authorR. Simpson, Tyleren_US
dc.contributor.authorS. Peggs, Karlen_US
dc.contributor.authorVider, Jelenaen_US
dc.contributor.authorYagita, Hideoen_US
dc.date.accessioned2017-04-04T22:58:55Z
dc.date.available2017-04-04T22:58:55Z
dc.date.issued2010en_US
dc.date.modified2012-05-15T22:38:29Z
dc.identifier.issn00221007en_US
dc.identifier.doi10.1084/jem.20091918en_US
dc.identifier.urihttp://hdl.handle.net/10072/44691
dc.description.abstractAdoptive transfer of large numbers of tumor-reactive CD8+ cytotoxic T lymphocytes (CTLs) expanded and differentiated in vitro has shown promising clinical activity against cancer. However, such protocols are complicated by extensive ex vivo manipulations of tumor-reactive cells and have largely focused on CD8+ CTLs, with much less emphasis on the role and contribution of CD4+ T cells. Using a mouse model of advanced melanoma, we found that transfer of small numbers of naive tumor-reactive CD4+ T cells into lymphopenic recipients induces substantial T cell expansion, differentiation, and regression of large established tumors without the need for in vitro manipulation. Surprisingly, CD4+ T cells developed cytotoxic activity, and tumor rejection was dependent on class II-restricted recognition of tumors by tumor-reactive CD4+ T cells. Furthermore, blockade of the coinhibitory receptor CTL-associated antigen 4 (CTLA-4) on the transferred CD4+ T cells resulted in greater expansion of effector T cells, diminished accumulation of tumor-reactive regulatory T cells, and superior antitumor activity capable of inducing regression of spontaneous mouse melanoma. These findings suggest a novel potential therapeutic role for cytotoxic CD4+ T cells and CTLA-4 blockade in cancer immunotherapy, and demonstrate the potential advantages of differentiating tumor-reactive CD4+ cells in vivo over current protocols favoring in vitro expansion and differentiation.en_US
dc.description.peerreviewedYesen_US
dc.description.publicationstatusYesen_US
dc.format.extent6466228 bytes
dc.format.mimetypeapplication/pdf
dc.languageEnglishen_US
dc.language.isoen_US
dc.publisherThe Rockefeller University Pressen_US
dc.publisher.placeUnited Statesen_US
dc.relation.ispartofstudentpublicationNen_US
dc.relation.ispartofpagefrom637en_US
dc.relation.ispartofpageto650en_US
dc.relation.ispartofissue3en_US
dc.relation.ispartofjournalJournal of Experimental Medicineen_US
dc.relation.ispartofvolume207en_US
dc.rights.retentionYen_US
dc.subject.fieldofresearchCancer Therapy (excl. Chemotherapy and Radiation Therapy)en_US
dc.subject.fieldofresearchcode111204en_US
dc.titleTumor-reactive CD4+ T cells develop cytotoxic activity and eradicate large established melanoma after transfer into lymphopenic hostsen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.rights.copyrightCopyright 2010 Rockefeller University Press. The attached file is reproduced here in accordance with the copyright policy of the publisher. Please refer to the journal's website for access to the definitive, published version.en_US
gro.date.issued2010
gro.hasfulltextFull Text


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