The role of neutrophils and TNF-related apoptosis-inducing ligand (TRAIL) in bacillus Calmette-Guérin (BCG) immunotherapy for urothelial carcinoma of the bladder

Cancer Metastasis Rev. 2009 Dec;28(3-4):345-53. doi: 10.1007/s10555-009-9195-6.


Intravesical Mycobacterium bovis bacillus Calmette-Guérin (BCG) immunotherapy is a highly effective treatment for carcinoma in situ of the bladder, as well as high-risk nonmuscle invasive urothelial carcinoma of the bladder. Despite over 30 years of clinical experience with BCG, the therapy's mechanism has remained enigmatic. Observations regarding the role of neutrophils in BCG immunotherapy have led to exciting discoveries regarding the potential role of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in creating the therapeutic benefit of BCG immunotherapy. In this paper, we will review the scope of the disease, highlight our understanding of the role for BCG in urothelial carcinoma of the bladder, explain the recent discoveries regarding the role of neutrophils and TRAIL in therapy, and theorize on potential future areas of research.

Publication types

  • Review

MeSH terms

  • Administration, Intravesical
  • Animals
  • Antigens, Bacterial / physiology
  • BCG Vaccine / administration & dosage
  • BCG Vaccine / pharmacology
  • BCG Vaccine / therapeutic use*
  • Carcinoma in Situ / drug therapy
  • Carcinoma in Situ / immunology
  • Carcinoma, Transitional Cell / drug therapy*
  • Carcinoma, Transitional Cell / immunology
  • Chemotaxis, Leukocyte / drug effects
  • Cytokines / physiology
  • Humans
  • Interferons / administration & dosage
  • Interferons / therapeutic use
  • Mice
  • Mice, Knockout
  • Models, Immunological
  • Neoplasm Invasiveness
  • Neutrophils / immunology*
  • Receptors, TNF-Related Apoptosis-Inducing Ligand / deficiency
  • Receptors, TNF-Related Apoptosis-Inducing Ligand / genetics
  • Receptors, TNF-Related Apoptosis-Inducing Ligand / physiology*
  • TNF-Related Apoptosis-Inducing Ligand / metabolism
  • TNF-Related Apoptosis-Inducing Ligand / physiology*
  • Th1 Cells / immunology
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / immunology
  • alpha-Crystallins / physiology


  • Antigens, Bacterial
  • BCG Vaccine
  • Cytokines
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • alpha-Crystallins
  • antigen 85, Mycobacterium bovis
  • Interferons