SIU 2017: Intravesical Immunomodulatory lmiquimod Enhances Bacillus Calmette Guérin (BCG) Down Regulation of Non-muscle invasive Bladder Cancer

Lisbon, Portugal (UroToday.com) Bacillus Calmette-Guérin (BCG) although not failure proof, has been the most efficient immunomodulatory treatment in the immunogenic non-muscle invasive bladder cancer (NMIBC) for the past 40 years. The authors investigated the role of immunomodulatory molecule Imiquimod through the main downstream molecules of mammalian Target of Rapamycin (mTOR) pathway and the BCG key receptors TLR 2 and TLR4 in NMIBC treatment.

Fischer 344 rats of 7 weeks of age received 4 weekly doses of 1.5mg N-methyl-n-nitrosourea (MNU) intravesically, for cancer induction. The animals were randomized in 4 groups (10/ group): a. CONTROL group (0.2 ml vehicle), b. BCG (106 cfu Connaught strain); c. Imiquimod (20mg/kg) and d. synergistic treatment BCG-Imiquimod. All groups were treated intravesically for a duration of 6 weeks, once a week. Upcon completion of treatemtn, the bladders were extracted and analyzed for histopathology, immunohistochemistry, cell proliferation (Ki-67), apoptosis (TUNEL), and immunoblotting: p-p70S6K, p-4E-BP1, TLR2 and TLR4 proteins.

Histopathology showed that BCG and Imiquimode decreased bladder tumorigenesis compared to Control group with proliferation decrease (Ki-67) and apoptosis increase (TUNEL). BCG upregulated TLR2 and Imiquimod upregulated TLR4 and downregulated p70S6K1.

The authors concluded that TLR7 agonist Imiquimod down-regulates bladder tumorigenesis through TLR4 and p70S6K, generating new perspectives to potentially boost BCG effects in the future.

Presented by: A. Camargo J
Affiliation: University of Campinas, Unicamp, Campinas, Brazil

Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre.Twitter: @GoldbergHanan at the 37th Congress of Société Internationale d’Urologie - October 19-22, 2017- Lisbon, Portugal

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