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Most of the anticancer compounds synthesized by chemists are primarily evaluated for their direct cytotoxic effects at the cellular level, often overlooking the critical role of the immune system. In this study, we developed a patient‐derived, T‐cell‐retaining tumor organoid model that allows us to evaluate the anticancer efficacy of chemical drugs under the synergistic paradigm of antigen‐specific T‐cell‐dependent killing, which may reveal the missed drug hits in the simple cytotoxic assay. We evaluated clinically approved platinum (Pt) drugs and a custom library of twenty‐eight PtIV compounds. We observed low direct cytotoxicity of Pt drugs, but variable synergistic effects in combination with immune checkpoint inhibitors (ICIs). In contrast, the majority of PtIV compounds exhibited potent tumor‐killing capabilities. Interestingly, several PtIV compounds went beyond direct tumor killing and showed significant immunosynergistic effects with ICIs, outstanding at sub‐micromolar concentrations. Among these, Pt‐19, PtIV compounds with cinnamate axial ligands, emerged as the most therapeutically potent, demonstrating pronounced immunosynergistic effects by promoting the release of cytotoxic cytokines, activating immune‐related pathways and enhancing T cell receptor (TCR) clonal expansion. Overall, this initiative marks the first use of patient‐derived immunocompetent tumor organoids to explore and study chemotherapy, advancing their path toward more effective small molecule drug discovery. [ABSTRACT FROM AUTHOR]

Introduction: Although immunotherapy works well in parts of patients with bladder cancer (BLCA), its overall response rate of anti-PD-1 inhibitors remains unsatisfactory. Besides, growing evidence shows that tumor-infiltrating lymphocytes (TILs) immunotherapy has demonstrated excellent efficacy in various cancers. Considering the huge heterogeneity and low overall survival rate of BLCA, it is urgent to explore the new immune checkpoints (ICs) or TILs therapy to improve the survival prognosis for BLCA patients. Materials and Methods: The public bioinformatics databases were used to explore the prognostic value of 5 potential ICs targets (TIM-3, LAG-3, OX40, 4– 1BB and CD39). A total of 46 BLCA patients undergoing surgical treatment at our hospital from May 2020 to October 2020 were enrolled in this study. The expressions of PD-1, TIM-3, LAG-3, OX40, 4– 1BB, and CD39 in T cells of BLCA patients were explored by flow cytometry, and the correlation between different subgroups of T cells and clinicopathological parameters was analyzed. Besides, the mouse CD4+CD39+ T cells, CD4+CD39- T cells, CD8+CD39+ T cells, and CD8+CD39- T cells were sorted and co-cultured with MB49 bladder cancer cell lines in vitro to investigate the potential biomarker of tumor-reactive TILs. Results: Public bioinformatics databases analyses show that only the high expression of CD39 was significantly associated with advanced tumor stage (P < 0.001) and tend to result in a worse survival rate. In our study, the elevated expression of CD39 in CD4+/CD8+ T cells were significantly associated with the pathological T stage (pT < 2, P = 0.041) and papillary tumor (P = 0.038). Moreover, the CD8+CD39+ T cells showed a stronger tumor-killing effect and produced a higher level of IFN-γ than other T cell populations. Conclusion: CD39 may be a potential prognostic marker in BLCA, and CD8+CD39+ T cells may be selected as tumor-reactive and killing T cells for TILs therapy. [ABSTRACT FROM AUTHOR]

Objective: To examine the effect of diagnostic ureteroscopy (URS) and ureteral access sheath usage on bladder recurrence following radical nephroureterectomy (RNU).Methods: We retrospectively reviewed the records of patients who underwent RNU between 2005 - 2019. Patients with a history of bladder cancer and those without a bladder cuff resection were excluded. Bladder recurrence was the primary outcome and cox regression modeling was used to assess the impact of URS adjusting for other factors.Results: Out of 271 RNU cases, 143 were included with a median age of 73 years (IQR 65 - 80). URS was performed in 104 cases (73%) and a ureteral access sheath was used in 26 (25%). With a median follow-up of 27 months, there were 36 (25%) bladder recurrences. The bladder recurrence rate (median time to recurrence) for patients who had URS vs no URS was 30.8% (9.0 months) and 7.7% (12.1 months), respectively (P = .02). A lower recurrence rate was noted in patients whom a ureteral access sheath was utilized (11.5%) vs those with no access sheath (39.7%, P = .01). Multivariable analysis revealed a significant increase in bladder recurrence if URS was performed prior to RNU (HR 5.6 [1.7 - 18.5], P <.004), however, this effect was mitigated if a ureteral access sheath was used (HR 1.3, [0.3 - 6.4], P = .76). Ureteral stent usage and performing a ureteroscopic biopsy had no significant effect on bladder recurrence.Conclusion: Diagnostic URS in patients undergoing RNU for UTUC significantly increases the risk of bladder recurrence. This effect may be mitigated by using a ureteral access sheath. [ABSTRACT FROM AUTHOR]

• Twenty-six percent of radical cystectomy patients experience acute kidney injury (AKI). • AKI is associated with higher length of hospital stay, complication, and readmissions. • Transfusion and continent diversion are independent predictors of AKI. • Complications increased at higher AKI stages when stratified by organ-system/type. To evaluate the incidence and predictors of early postoperative acute kidney injury (EP-AKI) during index hospitalization following radical cystectomy and its association with postoperative outcomes. All patients with bladder cancer who underwent radical cystectomy with intent-to-cure at our center between 2012 and 2020 were reviewed. EP-AKI during index hospitalization was evaluated using the Acute Kidney Injury Network criteria. The association between EP-AKI and demographics, clinicopathologic features, and perioperative outcomes, including length of hospital stay, complication rate, and readmission rate, were examined. A logistic regression analysis was performed to evaluate the predictors of EP-AKI. Overall, 435 patients met eligibility, of whom 112 (26%) experienced EP-AKI during index hospitalization (90 [21%] stage 1, 17 [4%] stage 2, and 5 [1%] stage 3). EP-AKI was associated with a longer mean operative time (6.8 vs. 6.1 hours; P < 0.001), higher mean length of hospital stay (6.3 vs. 5.6; P = 0.02), 30-day complication rate (71% vs. 51%; P < 0.001), 90-day complication rate (81% vs. 69%; P = 0.01) and 90-day readmission rate (37% vs. 33%; P = 0.04). The rate of complications increased at higher stages of AKI. On multivariable analysis, perioperative blood transfusion (OR: 1.84, P = 0.02) and continent diversion (OR: 3.29, P < 0.001) were independent predictors of EP-AKI. A quarter of cystectomy patients experience acute kidney injury during index hospitalization, which is associated with higher length of stay, postoperative complication, and readmission rates. Perioperative blood transfusion and continent diversion are independent predictors of such injury. [ABSTRACT FROM AUTHOR]