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.
Videira
Paula A
PA
Departamento de Imunologia, Faculdade de Ciências Médicas de Lisboa, Campo Mártires Da Pátria 130, Lisboa 1169-056 Portugal. paula.videira@fcm.unl.pt
Calais
Fernando M
FM
Correia
Manuela
M
Ligeiro
Dário
D
Crespo
Hélio J
HJ
Calais
Fernando
F
Trindade
Hélder
H
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