Immunotherapy of Cytotoxic T Cell-resistant Tumors by T Helper 2 Cells: An Exotaxin and STAT6-dependent Process

dc.contributor.authorMattes, Joergen_AU
dc.contributor.authorHulett, Marken_AU
dc.contributor.authorXie, Weien_AU
dc.contributor.authorHogan, Simonen_AU
dc.contributor.authorRothenberg, Marc Een_AU
dc.contributor.authorFoster, Paul Sen_AU
dc.contributor.authorParish, Christopheren_AU
dc.date.accessioned2015-12-13T23:14:15Z
dc.date.available2015-12-13T23:14:15Z
dc.date.issued2003
dc.date.updated2015-12-12T08:37:56Z
dc.description.abstractCurrently most attempts at cancer immunotherapy involve the generation of CD8+ cytotoxic T lymphocytes (CTLs) against tumor-associated antigens. Many tumors, however, have been immunoselected to evade recognition by CTLs and thus alternative approaches to cancer immunotherapy are urgently needed. Here we demonstrate that CD4+ T cells that recognize a secreted tumor-specific antigen and exhibit a cytokine secretion profile characteristic of Th2 cells, are capable of clearing established lung and visceral metastases of a CTL-resistant melanoma. Clearance of lung metastases by the Th2 cells was found to be totally dependent on the eosinophil chemokine, eotaxin, and partially dependent on the transcription activator signal transducer and activator of transcription 6 (STAT6), with degranulating eosinophils within the tumors inducing tumor regression. In contrast, tumor-specific CD4+ Th1 cells, that recruited macrophages into the tumors, had no effect on tumor growth. This work provides the basis for a new approach to adoptive T cell immunotherapy of cancer.
dc.identifier.issn0022-1007
dc.identifier.urihttp://hdl.handle.net/1885/88515
dc.publisherRockefeller University Press
dc.sourceJournal of Experimental Medicine
dc.subjectKeywords: CD4 antigen; CD8 antigen; cytokine; eotaxin; gamma interferon; interleukin 4; monoclonal antibody; ovalbumin; STAT6 protein; animal cell; animal model; article; cancer immunotherapy; controlled study; cytotoxic T lymphocyte; cytotoxicity; helper cell; mel Eosinophils; Eotaxin; Immune evasion; Th2 cells; Tumor immunotherapy
dc.titleImmunotherapy of Cytotoxic T Cell-resistant Tumors by T Helper 2 Cells: An Exotaxin and STAT6-dependent Process
dc.typeJournal article
local.bibliographicCitation.issue3
local.bibliographicCitation.lastpage393
local.bibliographicCitation.startpage387
local.contributor.affiliationMattes, Joerg, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationHulett, Mark, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationXie, Wei, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationHogan, Simon, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationRothenberg, Marc E, University of Cincinnati
local.contributor.affiliationFoster, Paul S, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationParish, Christopher, College of Medicine, Biology and Environment, ANU
local.contributor.authoremailu6900322@anu.edu.au
local.contributor.authoruidMattes, Joerg, t503
local.contributor.authoruidHulett, Mark, a261320
local.contributor.authoruidXie, Wei, u980656
local.contributor.authoruidHogan, Simon, u9301072
local.contributor.authoruidFoster, Paul S, u8800551
local.contributor.authoruidParish, Christopher, u6900322
local.description.notesImported from ARIES
local.description.refereedYes
local.identifier.absfor110709 - Tumour Immunology
local.identifier.ariespublicationMigratedxPub18223
local.identifier.citationvolume197
local.identifier.doi10.1084/jem.20021683
local.identifier.scopusID2-s2.0-0037415596
local.identifier.uidSubmittedByMigrated
local.type.statusPublished Version

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