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• W2113404235 abstract "Abstract Purpose: Targeting oncogenic receptors with antibodies has been thought to suppress tumor growth mainly by interrupting oncogenic signals. Recently, the essential role for adaptive immunity, and CD8+ T cells in particular, has been established as a major factor for anti-HER2/neu–mediated tumor regression. However, the role of CD4+ T cells is still being defined. The purpose of this study was to explore whether and to what extent CD4+ T cells are involved in mediating the effects of anti-HER2/neu therapy. Experimental Design: The role of CD4+ T cells was examined using a transplant model of the rat HER2/neu–overexpressing cell line TUBO. Tumor-bearing mice were treated with anti-neu therapy in conjunction with CD4 depletion or CD40L blockade. The effects of CD4 depletion on the antitumor response were examined by tumor growth analysis and enzyme-linked immunospot (ELISPOT). Results: In addition to CD8+ T cells, CD4+ T cells are also essential for anti-neu antibody-mediated tumor regression, but B cells are not required. The role for CD4+ cells is necessary throughout anti-neu therapy and not limited to helping CD8+ T cells. Expression of IFN-γ is necessary for anti-neu therapy and IFN-γ induces MHC-II expression in TUBO cells promoting direct recognition by CD4+ T cells. Furthermore, intratumoral depletion of CD4+ T cells or blockade of the activating cell-surface protein CD40L inhibits the antitumor response. Conclusions: This study reveals the essential role of CD4+ T cell for anti-neu–mediated tumor regression. Clin Cancer Res; 19(6); 1476–86. ©2013 AACR." @default.
• W2113404235 created "2016-06-24" @default.
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• W2113404235 date "2013-03-14" @default.
• W2113404235 modified "2023-10-16" @default.
• W2113404235 title "Effective Anti-Neu–Initiated Antitumor Responses Require the Complex Role of CD4+ T Cells" @default.
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• W2113404235 doi "https://doi.org/10.1158/1078-0432.ccr-12-2522" @default.
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