Characterisation of Bladder Cancer Dentritic Cells

Bacillus Calmette-Guerin (BCG) is the most effective intravesical therapy for superficial bladder cancer. It is hypothesised that BCG therapy has a local and systemic effect on antigen-presenting dendritic cells (DC) and that characteristics and variations in DC may reflect those of DC in cancer tissue. Blood, urine and tissue samples were taken from patients with bladder cancer before and during treatment with intravesical BCG. In blood the percentages and numbers of DC expressing maturation, co-stimulatory and intracellular cytokine markers were measured using flow cytometry. Immune responses in bladder cancer were monitored by the identification and characterisation of DC from the urine and tissue of patients with bladder cancer using flow cytometry, immunohistochemistry and electron microscopy. Significantly increased numbers of blood plasmacytoid DC in patients with T1 G3 bladder cancer decreased during BCG therapy so that after 6 treatments there were no differences in the number of blood DC in patients with stages of superficial bladder cancer. DC numbers expressing CD40 increased in the blood of patients treated with BCG. Numbers of DC expressing T helper 1 (Th1) cytokine increased in patients who did not develop an early recurrence of bladder cancer. Immature DC were identified in tissue and urine from patients with superficial bladder cancer and confirmed in samples of urine by immunohistochemistry and electron microscopy. BCG therapy decreased the percentage of DC in the urine of patients who subsequently had recurrent bladder cancer. The therapeutic effect of BCG may be mediated by normalising circulating numbers of plasmacytoid DC and by increasing numbers of DC expressing the costimulatory molecule CD40. In response to BCG therapy increased numbers of circulating Th1 cytokine (IL-12) expressing DC and increased percentages of urine DC may be crucial in preventing recurrent bladder cancer.EThOS - Electronic Theses Online ServiceGBUnited Kingdo