Molecular analyte profiling of the early events and tissue conditioning following intravesical bacillus calmette-guerin therapy in patients with superficial bladder cancer.
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.
Bisiaux
Aurélie
A
Laboratoire d'Immunobiologie des Cellules Dendritiques, Department of Immunology, Institut Pasteur, Paris, France.
Thiounn
Nicolas
N
Timsit
Marc-Olivier
MO
Eladaoui
Ahmed
A
Chang
Huey-Hsuan
HH
Mapes
James
J
Mogenet
Agnès
A
Bresson
Jean-Louis
JL
Prié
Dominique
D
Béchet
Stéphane
S
Baron
Camille
C
Sadorge
Christine
C
Thomas
Stéphanie
S
Albert
Elaine B
EB
Albert
Peter S
PS
Albert
Matthew L
ML
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
D000276:Adjuvants, Immunologic; D001500:BCG Vaccine