Efficacy of bacille Calmette-Guérin immunotherapy predicted by expression of antigen-presenting molecules and chemokines.
OBJECTIVE
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.
Departamento de Imunologia, Faculdade de Ciências Médicas de Lisboa, Campo Mártires Da Pátria 130, Lisboa 1169-056 Portugal. paula.videira@fcm.unl.pt
Paula A
PA
Videira
Fernando M
FM
Calais
Manuela
M
Correia
Dário
D
Ligeiro
Hélio J
HJ
Crespo
Fernando
F
Calais
Hélder
H
Trindade
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000368:Aged; D000369:Aged, 80 and over; D018949:Antigens, CD1 / Q000096:biosynthesis*; D001500:BCG Vaccine / Q000627:therapeutic use*; D005544:Forecasting; D006681:HLA-D Antigens / Q000096:biosynthesis*; D006801:Humans; D007167:Immunotherapy; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000517:prevention & control*
D000276:Adjuvants, Immunologic; D018949:Antigens, CD1; D001500:BCG Vaccine; D006681:HLA-D Antigens