Efficacy of Bacille Calmette-Guérin Immunotherapy Predicted by Expression of Antigen-presenting Molecules and Chemokines

• Published in: Urology (Ridgewood, N.J.) N.J.), 2009-10, Vol.74 (4), p.944-950
• Main Authors: Videira, Paula A, Calais, Fernando M, Correia, Manuela, Ligeiro, Dário, Crespo, Hélio J, Calais, Fernando, Trindade, Hélder
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - therapeutic use; Aged; Aged, 80 and over; Antigens, CD1 - biosynthesis; Bacterial diseases; BCG Vaccine - therapeutic use; Biological and medical sciences; Forecasting; HLA-D Antigens - biosynthesis; Human bacterial diseases; Humans; Immunotherapy; Infectious diseases; Medical sciences; Middle Aged; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - immunology; Neoplasm Recurrence, Local - prevention & control; Nephrology. Urinary tract diseases; Tuberculosis and atypical mycobacterial infections; Urinary Bladder Neoplasms - drug therapy; Urinary Bladder Neoplasms - immunology; Urinary Bladder Neoplasms - metabolism; Urinary Bladder Neoplasms - prevention & control; Urology
• ISSN: 0090-4295; 1527-9995
• DOI: 10.1016/j.urology.2009.02.053

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-1α, monocyte chemoattractant protein-1 and -2, interferon-inducible protein 10 kD (IP10), and monokine induced by γ-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.