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Superficial bladder tumors and increased reactivity against mycobacterial antigens before bacillus Calmette-Guerin
A R Zlotta1, A Drowart, J P Van Vooren
1Department of Urology, Erasme Hospital University Clinics of Brussels, Belgium.
Purpose:
The precise mechanism of action of bacillus Calmette-Guerin (BCG) in bladder cancer treatment remains poorly understood. Whether bladder 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 bladder cell tumors, we tested before BCG treatment the lymphoproliferation of peripheral blood lymphocytes against several mycobacterial antigens, including the secreted fibronectin binding antigen 85 complex from 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 extract, whole BCG, purified AG 85, and the nonspecific mitogens pokeweed and phytohemagglutinin was investigated in 79 patients with superficial bladder tumors before BCG and in 39 control subjects without malignancy matched for age and sex. Neither group had a history of tuberculosis. Lymphoproliferation was measured with a tritiated thymidine uptake assay on day 7 of culture.
Results:
Of the 79 patients with superficial transitional cell carcinoma, a significant lymphoproliferative response before BCG against PPD, BCG extract, whole BCG and AG 85 was observed 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 lymphoproliferation 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 lymphoproliferative levels, patients with superficial transitional cell carcinoma also showed a significantly higher response against PPD (p = 0.000012), BCG extract (p = 0.000001), AG 85 (p = 0.000001), whole BCG (p = 0.00001) and pokeweed (p = 0.01) than controls but not against phytohemagglutinin.
Conclusions:
Patients with superficial transitional cell carcinoma demonstrate an increased lymphoproliferation against mycobacterial antigens before BCG compared to control subjects. Although a nonspecific activation of the immune system cannot be excluded at this stage, our data may suggest the possible existence of bladder cancer antigens cross-reactive with mycobacterial antigens responsible for boosting precursor cells witnessing previous contacts with mycobacteria. The implication of these findings in the antitumoral mechanism of action of BCG are under investigation.
Insights
Patients with superficial bladder cancer show heightened immune cell activity against tuberculosis bacteria before treatment. This suggests a potential cross-reaction between bladder tumor antigens and mycobacterial antigens, influencing bacillus Calmette-Guerin (BCG) therapy effectiveness.
Area of Science:
- Immunology
- Oncology
- Microbiology
Background:
- The mechanism of action for bacillus Calmette-Guerin (BCG) in bladder cancer treatment is not fully understood.
- It is unclear if BCG destroys bladder tumors through non-specific immune responses or by activating lymphocytes that recognize specific tumor antigens.
Purpose of the Study:
- To investigate potential cross-reactivity between BCG and bladder tumor cells.
- To assess lymphoproliferation of peripheral blood lymphocytes against mycobacterial antigens before BCG treatment in bladder cancer patients.
Main Methods:
- A whole blood assay was used to measure T cell responses.
- Lymphoproliferation was assessed using a tritiated thymidine uptake assay on day 7.
- The study included 79 patients with superficial bladder tumors and 39 matched controls without malignancy.
Main Results:
- Patients with superficial transitional cell carcinoma exhibited significantly higher lymphoproliferative responses to purified protein derivative (PPD), BCG extract, whole BCG, and antigen 85 (AG 85) compared to controls.
- A notable percentage of bladder cancer patients (82.2% for PPD, 84.8% for BCG extract, 37.9% for whole BCG, 62.0% for AG 85) showed significant responses before treatment.
- Control subjects had significantly lower responses to these antigens.
Conclusions:
- Superficial transitional cell carcinoma patients demonstrate increased lymphoproliferation against mycobacterial antigens prior to BCG therapy.
- Findings suggest potential cross-reactivity between bladder cancer antigens and mycobacterial antigens, possibly boosting precursor cells from prior mycobacterial exposure.
- The implications for BCG's anti-tumoral mechanism are under ongoing investigation.