Depletion of CD4+CD25+ regulatory T cells enhances natural killer T cell‐mediated anti‐tumour immunity in a murine mammary breast cancer model

Journal article

Both invariant natural killer T (NK T) cells and CD4(+)CD25(+) T regulatory cells (T(regs)) regulate the immune system to maintain homeostasis. In a tumour setting, NK T cells activated by alpha-galactosylceramide (alpha-GalCer) execute anti-tumour activity by secreting cytokines. By contrast, T(regs) intrinsically suppress antigen-specific immune responses and are often found to be elevated in tumour patients. In this study, we have shown that T(regs) regulate NK T cell function negatively in vitro, suggesting a direct interaction between these cell types. In a murine mammary tumour model, we demonstrated that administration of either alpha-GalCer or anti-CD25 antibody alone markedly suppressed tumour formation and pulmonary metastasis, and resulted in an increase in the survival rate up to 44% (from a baseline of 0%). When treatments were combined, depletion of T(regs) boosted the anti-tumour effect of alpha-GalCer, and the survival rate jumped to 85%. Our results imply a potential application of combining T(reg) cell depletion with alpha-GalCer to stimulate NK T cells for cancer therapy.

Authors: Hong, H; Gu, Y; Zhang, H; Simon, A; Chen, X

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Wiley
• Journal: Clinical and Experimental Immunology
• Volume: 159
• Issue: 1
• Pages: 93-99
• Publication date: 2009-09-02
• Acceptance date: 2009-08-24
• DOI: 10.1111/j.1365-2249.2009.04018.x
• EISSN: 1365-2249
• ISSN: 0009-9104
• Pmid: 19817769
• Language: English
• Keywords: Interferon-gamma; Galactosylceramides; Lymphocyte Depletion; Antibodies, Monoclonal; Female; Journal Article; Mice, Inbred C57BL; Mice, Inbred BALB C; Mice; Mammary Neoplasms, Experimental; T-Lymphocytes, Regulatory; Lymphocyte Activation; Dendritic Cells; Natural Killer T-Cells; Interleukin-2 Receptor alpha Subunit; Immunity, Cellular; Animals; SBTMR; Disease Models, Animal; Survival Rate; Research Support, Non-U.S. Gov't; Lung Neoplasms