Evaluation of cellular tumour rejection mechanisms in the peritumoral bladder wall after bacillus Calmette‐Guérin treatment

Abstract

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-Gue Ârin (BCG). Patients and methods Twenty-three patients with super®cial 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 in®ltrating cell types, i.e. lymphocyte in®ltrates (CD4, CD8, CD20, CD3, interleukin-2-receptor-positive, natural killer, cd), 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 semiquantitative 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 ®rst course of BCG.

Milk fat globule—epidermal growth factor—factor VIII (MFGE8)/lactadherin promotes bladder tumor development

“…BCG instillation has been proposed to overcome the tolerance established in the tumor, and switch the immune system towards effective antitumor activity (Saint et al, 2001). Jinushi et al (Jinushi et al, 2007) have shown that, in the presence of pathogen-derived ligands and/or necrotic cells, phagocytosis of tumor cells by macrophages is performed in the absence of Mfge8 and results in effective anti-tumor immune responses, whereas in the absence of these stress conditions, the same phagocytosis performed through Mfge8 induces tolerogenic immune responses.…”

Interleukin-10 inhibitsMycobacterium bovisbacillus Calmette–Guérin (BCG)-induced macrophage cytotoxicity against bladder cancer cells

“…Several lines of evidence suggest that macrophages actively mediate BCG's anti-bladder cancer activity. Following BCG instillation, increased numbers of macrophages, along with T cells, natural killer (NK) cells and dendritic cells (DC), are observed in bladder cancer infiltrates and the peritumoral bladder wall [4,[7][8][9][10]. The voided urine of bladder cancer patients after BCG treatment also contains increased numbers of macrophages and other types of immune cells [11][12][13].…”

Effect of Different Bacillus Calmette-Guerin Substrains on Growth Inhibition of T24 Bladder Cancer Cells and Cytokines Secretion by BCG Activated Peripheral Blood Mononuclear Cells of PBMCs

“…As a result of intravesical administration of BCG increased numbers of granulocytes and mononuclear cells including macrophages, T cells, natural killer (NK) cells and dendritic cells (DC) infiltrate the bladder wall [8,[17][18][19]. Large amounts of immune cells [20,21] and secreted cytokines are also detected in the urine after intravesical BCG administration [22].…”