Efficacy of bacille Calmette-Guérin immunotherapy predicted by expression of antigen-presenting molecules and chemokines

Urology. 2009 Oct;74(4):944-50. doi: 10.1016/j.urology.2009.02.053. Epub 2009 May 9.

Abstract

Objectives: To ascertain the role and prognostic value of antigen-presenting molecules and chemokines in the prophylactic effect of intravesical bacille Calmette-Guérin (BCG) in tumor recurrence. We compared its gene expression in urothelium biopsy and tumor specimens from patients who had undergone BCG immunotherapy.

Methods: Patients with nonmuscle-invasive bladder cancer were divided into 3 groups, according to the cancer recurrence status: group 1, primary cancer without recurrence for a minimal period of 12 months; group 2, primary cancer with subsequent recurrence; and group 3, recurrent cancer at study entry. From each patient, cancerous bladder tissue and biopsy specimens of the urothelium (before and 3 months after transurethral resection of the bladder) were collected. The RNA levels of the antigen-presenting molecules CD1a, CD1b, CD1c, CD1d, CD1e, and major histocompatability complex-I, class I (MHC-I) and the chemokines macrophage inflammatory protein-1alpha, monocyte chemoattractant protein-1 and -2, interferon-inducible protein 10 kD (IP10), and monokine induced by gamma-interferon (MIG) were evaluated using real-time polymerase chain reaction on all samples.

Results: Generally, BCG treatment increased the urothelium expression of antigen-presenting molecules and chemokines. However, the differences for CD1a (P = .005), CD1b (P < .000), CD1c (P = .03), CD1e (P = .007), MHC-I (P < .000), MIG (P < .0001), and IP10 (P < .0001) were significantly superior in the BCG-treated urothelium of group 1 compared with the other groups. Tumor tissue from group 1 also had increased expression of MHC-I (P = .04) and contrasted with tumor tissue from group 3 with decreased expression of CD1c (P = .007) and CD1e (P = .02).

Conclusions: Patients without recurrence had greater increased urothelium expression of antigen-presenting molecules and chemokines after BCG treatment. These parameters might, therefore, serve to predict and monitor the efficacy of BCG immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / therapeutic use*
  • Aged
  • Aged, 80 and over
  • Antigens, CD1 / biosynthesis*
  • BCG Vaccine / therapeutic use*
  • Forecasting
  • HLA-D Antigens / biosynthesis*
  • Humans
  • Immunotherapy*
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / immunology
  • Neoplasm Recurrence, Local / prevention & control*
  • Urinary Bladder Neoplasms / drug therapy
  • Urinary Bladder Neoplasms / immunology
  • Urinary Bladder Neoplasms / metabolism*
  • Urinary Bladder Neoplasms / prevention & control*

Substances

  • Adjuvants, Immunologic
  • Antigens, CD1
  • BCG Vaccine
  • HLA-D Antigens