Effective Anti-Neu–Initiated Antitumor Responses Require the Complex Role of CD4+ T Cells
| Autor: | Yang Xin Fu, Eric D. Mortenson, Sae-Gwang Park, Zhujun Jiang, Shengdian Wang |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
CD4-Positive T-Lymphocytes
Cancer Research Receptor ErbB-2 T cell Mammary Neoplasms Animal CD8-Positive T-Lymphocytes Biology Antibodies Article Interferon-gamma Mice Interleukin 21 Cell Line Tumor medicine Animals Humans Cytotoxic T cell IL-2 receptor Antigen-presenting cell Interleukin 3 B-Lymphocytes ZAP70 Natural killer T cell Rats medicine.anatomical_structure Oncology Immunology Cancer research Immunotherapy |
| Zdroj: | Clinical Cancer Research. 19:1476-1486 |
| ISSN: | 1557-3265 1078-0432 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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