Urine dendritic cells: a noninvasive probe for immune activity in bladder cancer?

Abstract

Objectives: To test the hypothesis that dendritic cells (DC), antigen-presenting cells with the potential to stimulate primary T-cell responses, may appear in the urine of patients with bladder cancer, and that their characteristics may reflect those of DC in cancer tissue.

Patients and methods: Cells from digested tissue of transurethral resection specimens from eight patients and urine from 18 with bladder cancers were analysed using flow cytometry, immunohistochemistry and electron microscopy. Urine samples from 12 patients were also analysed during intravesical bacillus Calmette-Guerin (BCG) therapy.

Results: Immature DC positive for major histocompatibility complex class II antigens, negative for markers of other leukocyte lineages and with low levels of co-stimulatory markers, were identified in CD45-positive cells isolated immediately from cancer tissue or amongst cells migrating from tissue fragments after overnight culture. Immature-phenotype DC were also identified in the urine of patients with bladder cancer. Their identity was confirmed by immunohistochemistry and electron microscopy. Using these methods, DC were monitored from the bladder during BCG installation for bladder cancer in 12 patients for a mean of 10 months. Of six patients who developed a recurrence of their bladder cancer over this period, all but one showed a lower percentage of DC in their urine at the end of their initial treatment.

Conclusion: We identified DC in the urine of patients with bladder cancer for the first time. We speculate that variability in the percentage of urinary DC may reflect changes in immunological activity at the tumour site; prospective studies are required to evaluate the relevance of these DC counts and characteristics to clinical outcome.