title: Superficial bladder tumors and increased reactivity against mycobacterial antigens before bacillus Calmette-Guerin therapy.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Urology, Erasme Hospital University Clinics of Brussels, Belgium.
authors.forename: A R
authors.initials: AR
authors.lastname: Zlotta
authors.forename: A
authors.initials: A
authors.lastname: Drowart
authors.forename: J P
authors.initials: JP
authors.lastname: Van Vooren
authors.forename: H
authors.initials: H
authors.lastname: Shekarsarai
authors.forename: M
authors.initials: M
authors.lastname: De Cock
authors.forename: M
authors.initials: M
authors.lastname: Pirson
authors.forename: K
authors.initials: K
authors.lastname: Palfliet
authors.forename: F
authors.initials: F
authors.lastname: Jurion
authors.forename: J
authors.initials: J
authors.lastname: Simon
authors.forename: C C
authors.initials: CC
authors.lastname: Schulman
authors.forename: K
authors.initials: K
authors.lastname: Huygen
mesh_terms: D018829:Adhesins, Bacterial; D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000942:Antigens, Bacterial / Q000276:immunology*; D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology; D002295:Carcinoma, Transitional Cell / Q000276:immunology* / Q000628:therapy*; D002352:Carrier Proteins / Q000276:immunology; D003429:Cross Reactions; D005260:Female; D006360:Heat-Shock Proteins / Q000276:immunology; D006801:Humans; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009161:Mycobacterium / Q000276:immunology*; D001749:Urinary Bladder Neoplasms / Q000276:immunology* / Q000628:therapy*
chemical_list: D018829:Adhesins, Bacterial; D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D001500:BCG Vaccine; D001426:Bacterial Proteins; D002352:Carrier Proteins; D006360:Heat-Shock Proteins; C078635:fibronectin-binding proteins, bacterial