+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

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



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



Clinical and Experimental Immunology 159(1): 93-99



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.

(PDF emailed within 0-6 h: $19.90)

Accession: 052491425

Download citation: RISBibTeXText

PMID: 19817769

DOI: 10.1111/j.1365-2249.2009.04018.x


Related references

Combination of CTL-associated antigen-4 blockade and depletion of CD25 regulatory T cells enhance tumour immunity of dendritic cell-based vaccine in a mouse model of colon cancer. Scandinavian Journal of Immunology 71(2): 70-82, 2010

Depletion of regulatory T cells in tumors with an anti-CD25 immunotoxin induces CD8 T cell-mediated systemic antitumor immunity. Proceedings of the National Academy of Sciences of the United States of America 2019, 2019

Anti-tumor immunity induced by Interleukin-12 gene therapy in a metastatic model of breast cancer is mediated by natural killer cells. Breast Cancer Research & Treatment 60(2): 129-134, 2000

Depletion of CD4+CD25+ regulatory T cells enhances interleukin-2-induced antitumor immunity in a mouse model of colon adenocarcinoma. Cancer Science 98(3): 416-423, 2007

Systemic anti-CD25 monoclonal antibody administration safely enhances immunity in murine glioma without eliminating regulatory T cells. Clinical Cancer Research 12(14 Pt 1): 4294-4305, 2006

Depletion of regulatory T cells by anti-ICOS antibody enhances anti-tumor immunity of tumor cell vaccine in prostate cancer. Vaccine 35(43): 5932-5938, 2017

Depletion of CD4+ CD25+ regulatory T cells inhibits local tumour growth in a mouse model of B cell lymphoma. Clinical and Experimental Immunology 152(2): 381-387, 2008

Suppression of natural killer cell-mediated bone marrow cell rejection by CD4+CD25+ regulatory T cells. Proceedings of the National Academy of Sciences of the United States of America 103(14): 5460-5465, 2006

IL-7 Mediated Homeostatic Expansion of Human CD4+CD25+FOXP3+ Regulatory T Cells After Depletion With Anti-CD25 Monoclonal Antibody. Transplantation 100(9): 1853-1861, 2017

Partial depletion of natural CD4⁺CD25⁺ regulatory T cells with anti-CD25 antibody does not alter the course of acute influenza A virus infection. Plos One 6(11): E27849, 2012

Natural killer cell and hepatic cell interaction via NKG2A leads to dendritic cell-mediated induction of CD4 CD25 T cells with PD-1-dependent regulatory activities. Immunology 120(1): 73-82, 2006

Depletion of natural CD4 + CD25 + T regulatory cells with anti-CD25 antibody does not change the course of Pseudomonas aeruginosa -induced acute lung infection in mice. 2008

Depletion of natural CD4+CD25+ T regulatory cells with anti-CD25 antibody does not change the course of Pseudomonas aeruginosa-induced acute lung infection in mice. Immunobiology 214(3): 211-222, 2009

CD1d-expressing breast cancer cells modulate NKT cell-mediated antitumor immunity in a murine model of breast cancer metastasis. Plos One 6(6): E20702, 2011

A microparticle platform for STING-targeted immunotherapy enhances natural killer cell- and CD8 + T cell-mediated anti-tumor immunity. Biomaterials 205: 94-105, 2019