SUPERFICIAL BLADDER-TUMORS AND INCREASED REACTIVITY AGAINST MYCOBACTERIAL ANTIGENS BEFORE BACILLUS-CALMETTE-GUERIN THERAPY

Purpose: The precise mechanism of action of bacillus Calmette-Guerin ( BCG) in bladder cancer treatment remains poorly understood. Whether bl adder tumor cells are destroyed by nonspecific mechanisms or targeted by specifically activated lymphocytes recognizing cognate antigens is unclear. To investigate a possible cross-reactivity between BCG and bl adder cell tumors, we tested before BCG treatment the lymphoproliferat ion of peripheral blood lymphocytes against several mycobacterial anti gens, including the secreted fibronectin binding antigen 85 complex fr om BCG (AG 85) in patients with superficial bladder tumors compared to control matched patients. Materials and Methods: Using a whole blood assay, T cell response against purified protein derivative, BCG extrac t, whole BCG, purified AG; 85, and the nonspecific mitogens pokeweed a nd phytohemagglutinin was investigated in 79 patients with superficial bladder tumors before BCG and in 39 control subjects without malignan cy matched for age and sex. Neither group had a history of tuberculosi s. Lymphoproliferation was measured with a tritiated thymidine uptake assay on day 7 of culture. Results: Of the 79 patients with superficia l transitional cell carcinoma, a significant lymphoproliferative respo nse before BCG against PPD, BCG extract, whole BCG and AG 85 was obser ved in 65 (82.2%), 67 (84.81%), 30 (37.97%) and 49 (62.02%) patients, respectively. Of the 39 controls only 26 (64.1%), 23 (58.9%), 3 (7.7%) and 3 (7.7%) patients, respectively, had a significant lymphoprolifer ation against PPD, BCG extract, BCG and AG 85 (p > 0.05, p = 0.004, p = 0.00001 and p = 0.00001, respectively). In terms of lymphoproliferat ive levels, patients with superficial transitional cell carcinoma also showed a significantly higher response against PPD (p = 0.000012), BC G extract (p = 0.000001), AG 85 (p = 0.000001), whole BCG (p = 0.00001 ) and pokeweed (p = 0.01) than controls but not against phytohemagglut inin. Conclusions: Patients with superficial transitional cell carcino ma demonstrate an increased lymphoproliferation against mycobacterial antigens before BCG compared to control subjects. Although a nonspecif ic activation of the immune system cannot be excluded at this stage, o ur data may suggest the possible existence of bladder cancer antigens cross-reactive with mycobacterial antigens responsible for boosting pr ecursor cells witnessing previous contacts with mycobacteria. The impl ication of these findings in the antitumoral mechanism of action of BC G are under investigation.