EVALUATION OF LOCAL IMMUNE-RESPONSE AFTER INTRAVESICAL BACILLE CALMETTE-GUERIN TREATMENT FOR SUPERFICIAL BLADDER-CANCER

Objective To help define the optimal protocol of Bacille Calmette-Guer in (BCG) treatment for transitional cell carcinoma (TCC) of the bladde r by examining cytokine production and antigen presentation to effecto r cells after instillations of BCG in patients with bladder TCC. Patie nts and methods Sixty-four urine samples from 11 patients were tested for the production of interferon gamma (IFN-gamma) using a modified co mmercial enzyme-linked immunosorbent assay (ELISA) kit. Urine was coll ected before and at intervals up to 24 h after the intravesical instil lation of BCG. Immunohistological studies were also carried out using a two-step alkaline phosphatase technique to explore the expression of tumour-associated antigens (TAAs) (E7, 19A211, T138), major histocomp atibility complex (MHC) molecules and lymphocyte subset infiltrates (C D3, CD4, CD8) in bladder biopsies before and 3 weeks after the complet ion of treatment in seven patients. Results IFN-gamma was only detecte d 4, 6 and 8 h after instillation, with a maximum concentration at 6 h (2.9-34.7 IU/mL in 10 patients). During a 6-week course of BCG, IFN-g amma was barely detectable after the first two instillations, but grad ually increased from the third instillation onwards. TAA and MHC II an tigens, which were absent or faintly expressed on normal urothelial ce lls before treatment, were expressed strongly in five patients after t reatment. The local recruitment of immunocompetent cells was detected in all patients. Conclusion These results suggest that the local immun e response after the intravesical instillation of BCG can be quantifie d using simple ELISA tests and could be useful in defining objective c riteria for rationalizing treatment (dose and duration), and in determ ining the relation between the immune response and antitumour activity . There is evidence that antigen presentation is enhanced after BCG in stillations, suggesting that a T cell-MHC restricted pathway might be involved in the anti-tumour response. This study supports the search f or tumour-rejection antigens in bladder cancer.