Polarisation of a T helper cell immune response by CpG-containing oligonucleotides: A potential immunotherapy for bladder cancer

  1. Lookup NU author(s)
  2. Dr Helen Maitland
  3. Dr Barry Davies
  4. Professor John Kirby
  5. John Kelly
Author(s)Atkins H, Davies BR, Kirby JA, Kelly JD
Publication type Article
JournalBritish Journal of Cancer
Year2003
Volume89
Issue12
Pages2312-2319
ISSN (print)0007-0920
ISSN (electronic)1532-1827
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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.
PublisherNature Publishing Group
URLhttp://dx.doi.org/10.1038/sj.bjc.6601474
DOI10.1038/sj.bjc.6601474
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