Open AccessPatient‐derived renal cell carcinoma organoids for personalized cancer therapy
Author(s) -
Li Zhichao,
Xu Haibo,
Yu Lei,
Wang Jia,
Meng Qian,
Mei Hongbing,
Cai Zhiming,
Chen Wei,
Huang Weiren
Publication year - 2022
Publication title -
clinical and translational medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.125
H-Index - 1
ISSN - 2001-1326
DOI - 10.1002/ctm2.970
Subject(s) - organoid , chromophobe cell , renal cell carcinoma , cancer , cancer research , papillary renal cell carcinomas , kidney cancer , medicine , clear cell renal cell carcinoma , targeted therapy , personalized medicine , pathology , clear cell , biology , bioinformatics , microbiology and biotechnology
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.