2010
DOI: 10.1084/jem.20091918
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Tumor-reactive CD4+ T cells develop cytotoxic activity and eradicate large established melanoma after transfer into lymphopenic hosts

Abstract: Adoptive 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 lym… Show more

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Cited by 753 publications
(803 citation statements)
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“…105 However, in TC, the extent of tumor-infiltrating CD4 C cells does not appear to predict patient outcome. 90,102 No differences were found between PTC and MNG patients, with respect to tissue or peripheral blood CD4 C cell frequencies.…”
Section: Natural Killer T Cells (Nkt) Gd T Cells and Innate Lymphoidmentioning
confidence: 99%
“…105 However, in TC, the extent of tumor-infiltrating CD4 C cells does not appear to predict patient outcome. 90,102 No differences were found between PTC and MNG patients, with respect to tissue or peripheral blood CD4 C cell frequencies.…”
Section: Natural Killer T Cells (Nkt) Gd T Cells and Innate Lymphoidmentioning
confidence: 99%
“…There is growing interest in CD4 þ effector T cells with anticancer activity (16,17). In this report, we describe novel cellular interactions and resultant molecular mediators necessary for the development of a CD4 þ CTL population, which requires support from both DCs and NKT cells.…”
Section: Discussionmentioning
confidence: 98%
“…There are also reports of CD4 þ T cells orchestrating anticancer responses mediated by other effector populations such as macrophages (18,19) and NK cells (20). In addition, there are reports that CD4 þ T cells can display cytotoxic activity directly (16,17). This phenomenon has been observed mostly in chronic infections (21), but there is growing recognition of this population of cells in malignancy (22), including their detection in peripheral blood of patients with B-cell chronic lymphocytic leukemia (23).…”
Section: Discussionmentioning
confidence: 99%
“…CD4+ T cells may have an advantage over CD8 T cells simply since they are capable of recognizing tumor antigens via both MHCI and MHCII processing pathways, not just MHCI (Muranski and Restifo, 2009). Moreover, In recent years, it has been demonstrated that CD4+ T cells can also contribute to the eradication of cancers, such as melanoma, by actively killing tumor cells and activating macrophages (Quezada et al, 2010).…”
Section: Cd4+ T Cells Are Equally Important As Cd8+ Cellsmentioning
confidence: 99%