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Polarisation of a T-helper cell immune response by activation of dendritic cells with CpG-containing oligonucleotides: A potential therapeutic regime for bladder cancer immunotherapy

Lookup NU author(s): Helen Atkins, Dr Barry Davies, Emeritus Professor John Kirby, John Kelly


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Intravesical bacillus Calmette-Guerin (BCG) is a treatment for transitional cell carcinoma (TCC) and carcinoma in situ (cis) of the urinary bladder, but some patients remain refractory. The mechanism of cancer clearance is not known, but T cells are thought to play a contributory role. Tissue dendritic cells (DCs) are known to initiate antigen-specific immune responses following activation of receptors, which recognise molecular patterns on the surface of microorganisms. A family of these receptors, the toll-like receptors (TLRs), are also crucial for activating DC to produce cytokines that polarise the T-cell response towards a T helper (Th)1 or Th2 phenotype. This study compared the potential of intact BCG to activate DC with that of the defined TLR4 ligand lipopolysaccharide (LPS) and the TLR9 ligand CpG-oligonucleotide. It was found that all three stimuli efficiently activated normal DC, but cells expressing a mutant TLR4 responded poorly to stimulation with LPS. Importantly, stimulation with BCG induced both IL-12 and IL-10, suggesting subsequent development of a poorly focused T-cell immune response containing both Th1 and Th2 immune function. By contrast, LPS- and CpG-oligonucleotides induced only IL-12, indicating the potential to produce a Th1 response, which is likely to clear cancer most efficiently. Given the toxicity of LPS, our data suggest that CpG-oligonucleotides may be beneficial for intravesical therapy of bladder cancer. © 2003 Cancer Research UK.

Publication metadata

Author(s): Atkins H, Davies BR, Kirby JA, Kelly JD

Publication type: Article

Publication status: Published

Journal: British Journal of Cancer

Year: 2003

Volume: 89

Issue: 12

Pages: 2312-2319

Print publication date: 01/12/2003

ISSN (print): 0007-0920

ISSN (electronic): 1532-1827

Publisher: Nature Publishing Group


DOI: 10.1038/sj.bjc.6601474

PubMed id: 14676812


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