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dc.contributor.authorQuezada, Sergio A
dc.contributor.authorSimpson, Tyler R
dc.contributor.authorPeggs, Karl S
dc.contributor.authorMerghoub, Taha
dc.contributor.authorVider, Jelena
dc.contributor.authorFan, Xiaozhou
dc.contributor.authorBlasberg, Ronald
dc.contributor.authorYagita, Hideo
dc.contributor.authorMuranski, Pawel
dc.contributor.authorAntony, Paul A
dc.contributor.authorRestifo, Nicholas P
dc.contributor.authorAllison, James P
dc.date.accessioned2017-05-03T16:06:18Z
dc.date.available2017-05-03T16:06:18Z
dc.date.issued2010
dc.date.modified2012-05-15T22:38:29Z
dc.identifier.issn0022-1007
dc.identifier.doi10.1084/jem.20091918
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.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.format.extent6466228 bytes
dc.format.mimetypeapplication/pdf
dc.languageEnglish
dc.language.isoeng
dc.publisherThe Rockefeller University Press
dc.publisher.placeUnited States
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom637
dc.relation.ispartofpageto650
dc.relation.ispartofissue3
dc.relation.ispartofjournalJournal of Experimental Medicine
dc.relation.ispartofvolume207
dc.rights.retentionY
dc.subject.fieldofresearchCancer Therapy (excl. Chemotherapy and Radiation Therapy)
dc.subject.fieldofresearchMedical and Health Sciences
dc.subject.fieldofresearchcode111204
dc.subject.fieldofresearchcode11
dc.titleTumor-reactive CD4+ T cells develop cytotoxic activity and eradicate large established melanoma after transfer into lymphopenic hosts
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.rights.copyright© 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.
gro.date.issued2010
gro.hasfulltextFull Text
gro.griffith.authorVider, Jelena


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