Related Experiment Video
Updated: Aug 16, 2025
Culture of Bladder Cancer Organoids as Precision Medicine Tools
Published on: December 28, 2021
Patient-derived organoids potentiate precision medicine in advanced clear cell renal cell carcinoma
Yizheng Xue1, Bingran Wang2, Yiying Tao2
1Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
Abstract:
To investigate the role of patient-derived organoid (PDO) model in the precision medicine of advanced clear cell renal cell carcinoma (ccRCC), we retrospectively analyzed the clinical data of seven cases of ccRCC diagnosed by operation and pathology in Renji Hospital from September 2021 to September 2022. The seven patients were diagnosed with advanced ccRCC with or without remote metastasis. Cytoreductive and radical nephrectomy was performed respectively. To predict the response to immunotherapy and provide personalized medicine recommendation, a PDO model based on air-liquid interface system was established from the surgical resected tumor and subsequent drug screening was performed. Hematoxylin and eosin (H&E) staining and immunohistochemistry revealed that the PDO recapitulated the histological feature of parent tumor. Immunofluorescence staining identified that CD3+ T cells, SMA+ cancer associated fibroblasts, and CD31+ endothelial cells were preserved in PDO models. Fluorescence activated cell sorter (FACS) revealed an evidently increased ratio of CD8+/CD4+ T cells and apoptotic tumor cells in PDO treated with toripalimab than those treated with IgG4. The results showed that toripalimab is able to rescue the excessive death of CD8+ T cells by critically reversing the immune exhaustion state of ccRCC in PDO model. This research validated that PDO is a promising and faithful preclinical model for prediction of immunotherapy response in patients with ccRCC.
Insights
Patient-derived organoids (PDO) accurately model clear cell renal cell carcinoma (ccRCC) tumors. This preclinical model effectively predicts immunotherapy response, aiding precision medicine for advanced ccRCC.
Area of Science:
- Oncology
- Translational Medicine
- Biotechnology
Background:
- Advanced clear cell renal cell carcinoma (ccRCC) presents challenges for effective treatment.
- Precision medicine approaches are crucial for improving patient outcomes in ccRCC.
- Predictive preclinical models are needed to guide personalized therapy selection.
Purpose of the Study:
- To evaluate the utility of patient-derived organoids (PDO) as a model for precision medicine in advanced ccRCC.
- To assess the ability of PDO models to predict immunotherapy response.
- To investigate the potential of PDOs for personalized medicine recommendations in ccRCC.
Main Methods:
- Retrospective analysis of seven advanced ccRCC cases.
- Establishment of PDO models using an air-liquid interface system from surgical tumor resections.
- Drug screening and analysis of PDOs using Hematoxylin and eosin (H&E) staining, immunohistochemistry, immunofluorescence, and fluorescence-activated cell sorting (FACS).
Main Results:
- PDO models successfully recapitulated the histological features of the parent ccRCC tumors.
- Key cellular components including T cells, cancer-associated fibroblasts, and endothelial cells were preserved in PDOs.
- Treatment with toripalimab in PDO models increased the CD8+/CD4+ T cell ratio and tumor cell apoptosis, reversing immune exhaustion.
Conclusions:
- Patient-derived organoids serve as a faithful preclinical model for advanced ccRCC.
- PDOs demonstrate promise in predicting patient response to immunotherapy.
- This model supports the development of personalized medicine strategies for ccRCC patients.
