Background Bladder cancer is an important public health concern due to its prevalence, high risk of recurrence and associated cost of management. Although BCG instillation for urothelial cancer treatment is the gold-standard treatment for this indication, repeated BCG treatments are associated with significant toxicity and failure, underlining the necessity for alternative or complementary immunotherapy and overall for better understanding of T-cell responses generated within bladder mucosa. Tumor-infiltrating lymphocytes (TIL) have long been recognized as a crucial component of the tumor microenvironment for the control of tumor. Among TIL, unconventional γδ T cells sparked interest due to their potent antitumor functions. Although preclinical mouse xenograft models demonstrated the relevance of using γδ T cells as a novel therapy for bladder cancer (BCa), the contribution of γδ T cells in BCa patients’ pathology remains unaddressed. Methods Therefore, we first determined the proportion of intratumor γδ T cells in muscle-invasive patients with BCa by deconvoluting data from The Cancer Genome Atlas (TCGA) and the frequency of blood Vδ1, Vδ2, and total γδ T cells, by flow cytometry, from 80 patients with BCa (40 non-muscle and 40 muscle-invasive patients with BCa), as well as from 20 age-matched non-tumor patients. Then we investigated in vitro which treatment may promote BCa tumor cell recognition by γδ T cells. Results We observed a decrease of γδ T-cell abundance in the tumor compared with corresponding normal adjacent tissue, suggesting that the tumor microenvironment may alter γδ T cells. Yet, high intratumor γδ T-cell proportions were significantly associated with better patient survival outcomes, potentially due to Vδ2 T cells. In the blood of patients with BCa, we observed a lower frequency of total γδ, Vδ1, and Vδ2 T cells compared with non-tumor patients, similarly to the TCGA analysis. In addition, a favorable clinical outcome is associated with a high frequency of circulating γδ T cells, which might 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 (CD107a⁺) and cytokine-production (IFN-γ and TNF-α). Strikingly, combining BCG and Zoledronate treatments significantly elicited the most quantitative and qualitative response by increasing the frequency and the polyfunctionality of bladder tumor-reactive Vδ2 T cells. Conclusions Overall, our results suggest that (1) Vδ2 T cells might play a prominent role in bladder tumor control and (2) non-muscle invasive patients with BCa undergoing BCG therapy may benefit from Zoledronate administration by boosting Vδ2 T cells’ antitumor activity.

Despite the possible benefit from avoiding stone surgery with all its possible complications, oral chemolysis is rarely performed in patients with urinary stones suspected of uric acid content. Among the reasons for its limited use is the sparse and low-quality data on its efficacy and the lack of reliable factors predicting its outcome. We thus performed a retrospective single-center cohort study of 216 patients (median patient age 63 years) with 272 renal (48%) and/or ureteral (52%) stones treated with oral chemolysis from 01/2010 to 12/2019. Patients with low urine pH (< 6), low stone density upon non-contrast enhanced computed tomography (NCCT), radiolucent urinary stones on plain radiography, and/or a history of uric acid urolithiasis were included. Potassium citrate and/or sodium/magnesium bicarbonate were used for alkalization (target urine pH 6.5–7.2). Median stone size was 9 mm, median stone density 430 Hounsfield Units. Patients with ureteral stones < 6 mm were excluded since stones this small are very likely to pass spontaneously. The stone-free status of each patient was evaluated after 3 months using NCCT. Oral chemolysis was effective with a complete and partial response rate of stones at 3 months of 61% and 14%, respectively; 25% of stones could not be dissolved. Lower stone density (OR = 0.997 [CI 0.994–0.999]; p = 0.008) and smaller stone size (OR = 0.959 [CI 0.924–0.995]; p = 0.025) significantly increased the success rate of oral chemolysis in multivariate logistic regression analysis. More precise stone diagnostics to exclude non-uric-acid stones could further improve outcome.