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). PATIENTS AND 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.
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). PATIENTS AND 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.
Authors: Helen P Cathro; Mark E Smolkin; Dan Theodorescu; Vickie Y Jo; Soldano Ferrone; Henry F Frierson Journal: Cancer Immunol Immunother Date: 2009-09-16 Impact factor: 6.968