Changes in mucosal immune cells of bladder tumor patient after BCG intravesical immunotherapy

Abstract

The Bacillus Calmette-Guerin (BCG) is considered to be at least as effective, and perhaps superior to chemotherapy in the prophylaxis of recurrent superficial tumors. However, the mechanism of the antitumor effect of BCG is still not exactly known. We have conducted investigations to examine changes in bladder mucosal immune cells in patients with superficial bladder carcinoma treated with a first cycle of BCG. The study group included 15 BCG and 5 doxorubicin instillation patients, most in the intermediate or high risk group for recurrent tumor. Grossly normal bladder mucosal cold cup biopsies were performed at initial TUR and one week after six consecutive weekly instillations of BCG or doxorubicin. All specimens underwent immunohistochemical staining, both pre-treatment and post-treatment, including CD20, CD45RO, CD8, CD4 and CD57. Immunoreactive cell counts were evaluated from three different microscopic fields (x400) under the grid. The mean duration of follow-up was 52.8 months. The post-treatment bladder mucosal B-cells (CD20) and T-cells (CD45RO, CD4, CD8) were significantly increased compared to pre-treatment in patients treated with BCG instillation, but NK-cells (CD57) were not changed. However, there was no change in B-cells or T-cells in patient treated with doxorubicin. The CD20 cells in pre-treatment specimens did not correlate with any other cells. However, it was a statistically significant correlation with CD45RO in post-treatment specimens. The CD4 correlated with CD45RO and CD8 in pre-treatment, but it was correlated with CD45RO and CD57 in post-treatment specimens. There was no tumor recurrence in cases with significantly increased B-cells after BCG instillation. The results of these studies suggest that intravesical BCG immunotherapy for superficial bladder tumor induces a significant increase in T-cells as well as B-cells and that B-cells have a preventive effect on tumor recurrence. Further studies with a larger number of patients are needed to confirm the value of the B-cell increment after BCG instillation as a clinically independent prognostic factor.