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Patient-derived renal cell carcinoma organoids for personalized cancer therapy
Zhichao Li1,2,3, Haibo Xu1,2,3, Lei Yu2
1Department of Urology, Shenzhen Institute of Translational Medicine, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, International Cancer Center, Shenzhen University School of Medicine, Shenzhen, China.
Background:
Kidney cancer is one of the most common solid tumors. The advancement of human kidney cancer research and treatment has been hindered by a lack of research models that faithfully recapitulate the diversity of the disease.
Methods:
We established an effective three-dimensional culture system for generating kidney cancer organoids from clinical renal cell carcinoma samples. Renal cell carcinoma (RCC) organoids were characterized by H&E staining, immunofluorescence, whole-exome sequencing, RNA sequencing and single-cell RNA sequencing. The use of RCC organoids in personalized cancer therapy was assessed by testing their responses to treatment drugs and chimeric antigen receptor T cells.
Results:
Using this organoid culture system, 33 kidney cancer organoid lines from common kidney cancer subtypes, including clear cell renal cell carcinoma (ccRCC), papillary renal cell carcinoma (pRCC), and chromophobe renal cell carcinoma (chRCC), were generated. RCC organoids preserved the histological architectures, mutational landscapes, and transcriptional profile of the parental tumor tissues. Single-cell RNA-sequencing revealed inter- and intra-tumoral heterogeneity in RCC organoids. RCC organoids allowed for in vitro drug screening and provided a tool for assessing the efficacy of chimeric antigen receptor T cells.
Conclusions:
Patient-derived RCC organoids are valuable pre-clinical models for academic research and personalized medicine.
Insights
Researchers developed kidney cancer organoids from patient tumors. These models accurately reflect diverse kidney cancers and aid in drug screening and personalized treatment strategies.
Area of Science:
- Oncology
- Translational Medicine
- Biotechnology
Background:
- Kidney cancer is a common solid tumor with diverse subtypes.
- Current research is limited by a lack of models that capture disease heterogeneity.
- Effective models are crucial for advancing kidney cancer research and treatment.
Purpose of the Study:
- To establish a 3D culture system for generating kidney cancer organoids from clinical samples.
- To characterize these organoids for their fidelity to the original tumors.
- To evaluate the utility of organoids in personalized cancer therapy.
Main Methods:
- Developed a 3D culture system for renal cell carcinoma (RCC) organoids.
- Characterized organoids using histology, immunofluorescence, and multi-omics (WES, RNA-seq, scRNA-seq).
- Assessed organoid response to drugs and CAR T-cell therapy for personalized treatment evaluation.
Main Results:
- Generated 33 kidney cancer organoid lines across major subtypes (ccRCC, pRCC, chRCC).
- Organoids retained histological, mutational, and transcriptional features of primary tumors.
- Single-cell RNA-seq confirmed inter- and intra-tumoral heterogeneity.
- Organoids enabled in vitro drug screening and CAR T-cell efficacy assessment.
Conclusions:
- Patient-derived RCC organoids are effective pre-clinical models.
- These organoids represent a significant advancement for kidney cancer research.
- Organoids offer a valuable platform for personalized medicine approaches.
