Evaluation of cellular tumour rejection mechanisms in the peritumoral bladder wall after bacillus Calmette-Guérin treatment.
OBJECTIVE
To compare the immunological status of normal and peritumoral bladder walls, and to characterize immunocompetent cells before and during intravesical instillations of bacillus Calmette-Guérin (BCG).


METHODS
Twenty-three patients with superficial urothelial bladder carcinoma (stages pTa to pT1, grades 1-3) were treated with six weekly instillations of 150 mg of BCG (Pasteur strain). Biopsies of cystoscopically normal bladder wall were taken before, 3 weeks and 3 months after BCG instillation. The controls comprised bladder biopsy specimens from 13 brain-dead ventilated kidney donors. Local infiltrating cell types, i.e. lymphocyte infiltrates (CD4, CD8, CD20, CD3, interleukin-2-receptor-positive, natural killer, gammadelta), macrophages and dendritic cells, adhesion and costimulatory molecules (ICAM-1 and B7-BB1) and major histocompatibility complex (MHC) class I and class II antigens were assessed using semi-quantitative immunohistochemical analysis.


RESULTS
Before BCG the peritumoral bladder wall had fewer macrophages than control bladder wall. BCG treatment restored normal numbers of macrophages and enhanced T helper lymphocytes, B lymphocytes, natural killer cells, activated lymphocytes, dendritic cells, normal MHC class I, adhesion (ICAM-1) and costimulatory (B7-BB1) expression. The enhancement of these immunological variables was transient, with a return to baseline 3 months after BCG instillation.


CONCLUSIONS
These results support the concept that there is a host-immune escape associated with bladder cancer. BCG therapy may temporarily restore impaired tumour rejection mechanisms in the peritumoral bladder wall, suggesting a need for maintenance therapy after the first course of BCG.
Saint
F
F
Department of Urology, Hôpital Henri Mondor, Créteil, France.
Patard
J J
JJ
Groux Muscatelli
B
B
Lefrere Belda
M A
MA
Gil Diez de Medina
S
S
Abbou
C C
CC
Chopin
D K
DK
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000918:Antibody Specificity; D001706:Biopsy; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D016867:Immunocompromised Host; D007150:Immunohistochemistry; D016131:Lymphocyte Subsets / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009163:Mycobacterium bovis / Q000276:immunology*; D009367:Neoplasm Staging; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D001743:Urinary Bladder / Q000276:immunology*; D001749:Urinary Bladder Neoplasms / Q000276:immunology* / Q000628:therapy