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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.
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
URL: http://dx.doi.org/10.1038/sj.bjc.6601474
DOI: 10.1038/sj.bjc.6601474
PubMed id: 14676812
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