Depletion of CD4+CD25+ regulatory T cells enhances natural killer T cell-mediated anti-tumour immunity in a murine mammary breast cancer model.
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.
Hong
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School of Pharmaceutical Science, Sun-Yet-Sen University, Guangzhou, China.
Gu
Y
Y
Zhang
H
H
Simon
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AK
Chen
X
X
Wu
C
C
Xu
X-N
XN
Jiang
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S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005699:Galactosylceramides / Q000276:immunology / Q000627:therapeutic use; D007111:Immunity, Cellular / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D008175:Lung Neoplasms / Q000473:pathology / Q000517:prevention & control / Q000556:secondary; D008213:Lymphocyte Activation / Q000276:immunology; D008212:Lymphocyte Depletion; D008325:Mammary Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism; D015996:Survival Rate; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects / Q000276:immunology*
D000911:Antibodies, Monoclonal; D005699:Galactosylceramides; C508018:Il2ra protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; C493154:alpha-galactosylceramide; D007371:Interferon-gamma