(UroToday.com) Bladder cancer (BCa) is a public health concern due to its prevalence and high risk of recurrence. Although Bacillus Calmette-Guérin (BCG) instillation is the gold standard treatment for urothelial carcinoma, such treatment is associated with significant side-effects and failure, underlying the necessity for alternative immunotherapy. Tumor infiltrating lymphocytes (TIL) are a crucial component for controlling tumor growth. Among TIL, γδ T cells sparked interest due to their potent anti-tumor functions. Notably, mouse xenograft models demonstrated the relevance of using γδ T cells as a novel therapy for BCa, but the contribution of γδ T cells in BCa patients remains unaddressed.
They determined the proportion of intratumor γδ T cells in muscle invasive BCa patients from The Cancer Genome Atlas (TCGA) and the frequency of blood Vδ1, Vδ2, and total γδ T cells, by flow cytometry, from 40 non-muscle and 40 muscle invasive BCa patients, as well as 20 non-tumor patients. Finally, they investigated in vitro whether treatment could promote BCa tumor cell recognition by Vδ2 T cells.
In the TGCA analysis, they found a decrease of γδ T cells in the tumor compared to normal adjacent tissue. Yet, a high intratumor γδ T-cell proportion was associated with improved survival. In the blood of BCa patients, they also observed a lower frequency of total γδ, Vδ1, and Vδ2 T cells compared to non-tumor patients. Similarly to the TCGA analysis, a favorable clinical outcome is associated with a high frequency of γδ T cells, which may be mainly attributed to the Vδ2 T-cell subset. Furthermore, in vitro assays revealed that either BCG, Zoledronate, or anti-BTN3 agonistic antibody treatment of bladder tumor cells induced Vδ2 T-cell cytolytic and cytokine production. Strikingly, combining BCG and Zoledronate treatments elicited the most potent response by increasing the frequency and the polyfunctionality of bladder tumor-reactive Vδ2 T cells.
Overall, these results suggest that Vδ2 T cells may play a prominent role in bladder tumor control, and non-muscle invasive BCa patients undergoing BCG therapy may benefit from Zoledronate administration by boosting Vδ2 T cells anti-tumor activity.
Presented by: Sylvain Nguyen, MS, BS, PhD Student, University of Lausanne, Lausanne, Switzerland
Written by: Stephen B. Williams, MD, MBA, MS @SWilliams_MD on Twitter during the International Bladder Cancer Network Annual Meeting, September 28-October 1, 2022, Barcelona, Spain