title: Molecular analyte profiling of the early events and tissue conditioning following intravesical bacillus calmette-guerin therapy in patients with superficial bladder cancer.
abstract: OBJECTIVE
  We characterized the innate immune response to intravesical bacillus Calmette-Guerin therapy using a systems approach based on proteomic and cytometric screens.
  
  
  METHODS
  Blood and urine were collected from patients receiving intravesical bacillus Calmette-Guerin therapy before, and 2 and 4 hours after bacillus Calmette-Guerin treatment, at the first and third instillation. Proteomic and cytometry based screens were performed.
  
  
  RESULTS
  Molecular analyte profiling revealed a prime/boost pattern to the innate response to intravesical bacillus Calmette-Guerin. We identified 36 statistically significant changes in the proteins induced during the third instillation compared to the initial treatment. These analytes were classified into 3 categories of 1) plasma proteins that leaked into the urine, 2) cytokines/chemokines produced locally during the first hours of inflammation and 3) other innate molecules that modulate the bladder microenvironment. To characterize the marked increase in the inflammatory response after multiple treatments we evaluated the cells present in the urine and again a prime/boost response was revealed. For the locally produced analytes it was possible to define the cell source(s) and, thus, provide a first generation map of what occurs during the initial phase of bacillus Calmette-Guerin therapy.
  
  
  CONCLUSIONS
  This study provides in vivo information concerning the ability of bacillus Calmette-Guerin to sensitize the tissue microenvironment to enhance innate responses and establishes a framework for improving vaccination strategies while decreasing adverse events.
authors.affiliation: Laboratoire d'Immunobiologie des Cellules Dendritiques, Department of Immunology, Institut Pasteur, Paris, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Bisiaux
authors.forename: Nicolas
authors.initials: N
authors.lastname: Thiounn
authors.forename: Marc-Olivier
authors.initials: MO
authors.lastname: Timsit
authors.forename: Ahmed
authors.initials: A
authors.lastname: Eladaoui
authors.forename: Huey-Hsuan
authors.initials: HH
authors.lastname: Chang
authors.forename: James
authors.initials: J
authors.lastname: Mapes
authors.forename: Agnès
authors.initials: A
authors.lastname: Mogenet
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Bresson
authors.forename: Dominique
authors.initials: D
authors.lastname: Prié
authors.forename: Stéphane
authors.initials: S
authors.lastname: Béchet
authors.forename: Camille
authors.initials: C
authors.lastname: Baron
authors.forename: Christine
authors.initials: C
authors.lastname: Sadorge
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Thomas
authors.forename: Elaine B
authors.initials: EB
authors.lastname: Albert
authors.forename: Peter S
authors.initials: PS
authors.lastname: Albert
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Albert
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000283:Administration, Intravesical; D000368:Aged; D001500:BCG Vaccine / Q000008:administration & dosage*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D040901:Proteomics; D013997:Time Factors; D001749:Urinary Bladder Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000652:urine
chemical_list: D000276:Adjuvants, Immunologic; D001500:BCG Vaccine