217P - Conditional reprogramming of urine-derived bladder cancer cells: A model for precision medicine

Background

With conditional reprogramming (CR) technique to generate continuous primary cancer cell cultures from bladder cancer patients’ urine samples, we aimed to establish a novel in vitro model by a rapid and non-invasive method to predict clinical response to anti-tumor drugs including immunotherapy and provide drug guidance for patients.

Methods

Patients included were all diagnosed with bladder cancer, among which were 54 high grade and 14 low grade. Urine and tumor samples were collected before therapeutic treatment. The overall success rate was summarized. Whole-exome sequencing (WES) and short tandem repeat (STR) analysis were utilized to confirm the authentication of CR cultures (CRCs). Dose-response measurements were used to generate drug sensitivity scores. Expression of PD-L1 on the cell surface of urine CRCs after IFN-γ treatment is evaluated with flow cytometry.

Results

The overall success rate of establishing urine CRCs was 87.2% (68/78), with 93.1% (54/58) of high grade bladder cancer, 70.0% (14/20) of low grade bladder cancer. Importantly, the in vitro drug sensitivity results of the urine-derived cells exhibited strong consistency (78%) with the clinical responses to treatment, indicating their potential for guiding patient-specific therapeutic strategies. Furthermore, we revealed that IFN-γ-stimulated PD-L1 expression on urine CRCs could predict the prognosis of bladder cancer patients and exhibited predictive value for ICI response in bladder cancer patients with a significant consistency of 88%, highlighting their clinical relevance.

Conclusions

Our study demonstrates the successful establishment of a reliable and patient-specific bladder cancer cell model derived from urine samples which serve to guide anti-tumor drugs and immunotherapeutic interventions. The findings underscore the clinical utility and translational potential of urine-derived cells for personalized bladder cancer management.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Zhongshan Hospital Fudan University.

Funding

National Natural Science Foundation of China.

Disclosure

All authors have declared no conflicts of interest.