SUO 2019: Immunotherapy in Bladder Cancer: Targets and Surgical Timing

Washington, DC (UroToday.com) As part of the Research Scholars Update at the 20th Annual Meeting of the Society of Urologic Oncology, Dr. Karen Wheeler presented her work on immunotherapy and bladder cancer. Previous work has shown that surgery can induce an immune suppressive state. Using a mouse model, Dr. Wheeler assessed survival of mice with intravenous MB49 (lung metastasis) or intravesical MB49 (orthotopic) demonstrating that surgery can worsen survival in the metastatic model but not in an orthotopic (bladder cancer) model:

SUO19_bladder_cancer_model.png

But the questions that remain include:

  • What T cell subsets are involved?
  • Are there differences in phenotypes in the bladder and lungs?

Using intravesical MB49 mice and treating them on day 7, day 11, and day 15 with 50 ug/kg of diphtheria toxin, Dr. Wheeler found a massive depletion of Treg cells in bladder cancer.

SUO19_Treg_cells.png

Ongoing work includes understanding the mechanism of Treg “protection” of bladder cancer and attempting intravesical use of Treg-depleting molecules.

Dr. Wheeler’s second project assessed the timing of immunotherapy and surgery. Mice with MB49-met subsequently had surgery to remove their tumor when it grew to 1000 mm3 and found that 50% of mice had died by 40 days and all had died by 60 days. Subsequently, the timing of immunotherapy in both the neoadjuvant and adjuvant setting was tested. MB49 mice were treated on day 14, 17 and 20 with anti-PD-L1, followed by surgery to remove their tumor at day 24. For the adjuvant mice, they had surgery at day 14 followed by anti-PD-L1 therapy at days 20, 23, and 27. What they found is that timing of immunotherapy did not matter in that both groups of mice did similarly better than controls:

SUO19_anti-PD-L1.png

Dr. Wheeler summarized her talk with the following take home points:

  • Surgical stress does not appear to affect the intravesical MB49 model of bladder cancer.
  • Treg plays a pivotal role in bladder cancer and targeting Treg or their mechanism of action could lead to novel therapeutics.
  • Surgery alone improves survival in mice with bladder cancer, whereby neoadjuvant treatment with anti-PD-L1 may slightly improve survival.

Presented by: Karen M. Wheeler, MD, Urologist, UT Health San Antonio, San Antonio, Texas, USA.

Written By: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia Twitter: @zklaassen_md at the 20th Annual Meeting of the Society of Urologic Oncology (SUO), December 4 - 6, 2019, Washington, DC

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