Journal
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
Volume 159, Issue 1, Pages 93-99Publisher
WILEY
DOI: 10.1111/j.1365-2249.2009.04018.x
Keywords
alpha-galactosylceramide; anti-tumour immunity; CD4+CD25+regulatory T cells; innate; natural killer T cells
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Funding
- Guangdong Science and Technology
- Mary Kinross Charitable Trust's Fund
- MRC [MC_U137881015] Funding Source: UKRI
- Medical Research Council [G1000800j, MC_U137881015] Funding Source: researchfish
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P>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.
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