Individualized patient tumor organoids faithfully preserve human brain tumor ecosystems and predict patient response to therapy

doi:10.1016/j.stem.2025.01.002

	Individualized patient tumor organoids faithfully preserve human brain tumor ecosystems and predict patient response to therapy
	Tianping Peng1,2,23 ; Xiujian Ma 3,23; Wei Hua 4,23; Changwen Wang 3; Youjun Chu1 ; Meng Sun1,2 ; Valentina Fermi 5; Stefan Hamelmann 6; Katharina Lindner 7,16,17; Chunxuan Shao 3; Julia Zaman 6; Weili Tian 3; Yue Zhuo 3; Yassin Harim 3; Nadja Stöffler 3; Linda Hammann 3; Qungen Xiao 3; Xiaoliang Jin 3; Rolf Warta 5; Catharina Lotsch 5; Xuran Zhuang2 ; Yuan Feng 4; Minjie Fu 4; Xin Zhang 4; Jinsen Zhang 4; Hao Xu 4; Fufang Qiu 4; Liqian Xie 4; Yi Zhang 4; Wei Zhu 4; Zunguo Du 22; Lorena Salgueiro 8,18,19; Mark Schneider 9,20; Florian Eichhorn 10,20; Arthur Lefevre 11; Stefan Pusch 6; Valery Grinevich 11; Miriam Ratliff 12; Sonja Loges 8,18,19,20; Lukas Bunse 7,16,17; Felix Sahm 6; Yangfei Xiang2,13,14 ; Andreas Unterberg 5; Andreas von Deimling 6; Michael Platten 7,15,16,17,21; Christel Herold-Mende 5; Wu, Yonghe (吴永和)1 ; Hai-Kun Liu1,3,24 ; Ying Mao 4
	2025-02-11
发表期刊	CELL STEM CELL (IF:19.8[JCR-2023],22.6[5-Year])
ISSN	1875-9777
发表状态	已发表
DOI	10.1016/j.stem.2025.01.002
摘要	Abstract Tumor organoids are important tools for cancer research, but current models have drawbacks that limit their applications for predicting response to therapy. Here, we developed a fast, efficient, and complex culture system (IPTO, individualized patient tumor organoid) that accurately recapitulates the cellular and molecular pathology of human brain tumors. Patient-derived tumor explants were cultured in induced pluripotent stem cell (iPSC)-derived cerebral organoids, thus enabling culture of a wide range of human tumors in the central nervous system (CNS), including adult, pediatric, and metastatic brain cancers. Histopathological, genomic, epigenomic, and single-cell RNA sequencing (scRNA-seq) analyses demonstrated that the IPTO model recapitulates cellular heterogeneity and molecular features of original tumors. Crucially, we showed that the IPTO model predicts patient-specific drug responses, including resistance mechanisms, in a prospective patient cohort. Collectively, the IPTO model represents a major breakthrough in preclinical modeling of human cancers, which provides a path toward personalized cancer therapy.
关键词	brain metastasis glioblastoma patient tumor organoid predictive patient model temozolomide tumor heterogeneity
学科门类	理学::生物学 ; 医学 ; 医学::基础医学（可授医学、理学学位）
URL	查看原文
语种	英语
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/487150
专题	生命科学与技术学院生命科学与技术学院_博士生免疫化学研究所_特聘教授组_刘海坤组生命科学与技术学院_PI研究组_向阳飞组
共同第一作者	Xiujian Ma; Wei Hua
通讯作者	Wu, Yonghe (吴永和); Hai-Kun Liu; Ying Mao
作者单位	1.Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University; Shanghai Clinical Research and Trial Center, Shanghai 201210, China 2.School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China 3.Division of Molecular Neurogenetics, German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance, Im Neuenheimer Feld 581, Heidelberg 69120, Germany 4.Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University; National Center for Neurological Disorders, Shanghai 200040, China 5.Division of Experimental Neurosurgery, Department of Neurosurgery, University Hospital Heidelberg, INF400, Heidelberg 69120, Germany 6.Deptment of Neuropathology, University Hospital Heidelberg, CCU Neuropathology, German Cancer Research Center (DKFZ), University Heidelberg, Heidelberg 69120, Germany 7.DKTK Clinical Cooperation Unit (CCU) Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany 8.DKFZ-Hector Cancer Institute at the University Medical Center Mannheim, Mannheim 68167, Germany 9.Translational Research Unit, Thoraxklinik at Heidelberg University, Heidelberg 69120, Germany 10.Department of Thoracic Surgery, Thoraxklinik, University Hospital Heidelberg, Roentgenstrasse 1, Heidelberg 69126, Germany 11.Department of Neuropeptide Research in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim 68167, Germany 12.DKTK Clinical Cooperation Unit (CCU) Neurooncology, German Cancer Research Center (DKFZ), Department of Neurosurgery, University Hospital Mannheim, University of Heidelberg, Mannheim 68167, Germany 13.State Key Laboratory of Advanced Medical Materials and Devices, ShanghaiTech University, Shanghai 201210, China 14.Shanghai Clinical Research and Trial Center, Shanghai 201210, China 15.DKFZ Hector Cancer Institute at the University Medical Center Mannheim, Helmholtz Institute of Translational Oncology Mainz (HI-TRON Mainz) - a Helmholtz Institute of the DKFZ, Mainz 55131, Germany 16.Department of Neurology, Medical Faculty Mannheim, Mannheim Center for Tanslational Neuroscience (MCTN), Heidelberg University, Heidelberg 69120, Germany 17.Immune Monitoring Unit, National Center for Tumor Diseases (NCT), Heidelberg 69120, Germany 18.Division of Personalized Medical Oncology (A420), German Cancer Research Center (DKFZ), Heidelberg 69120, Germany 19.Department of Personalized Oncology, University Hospital Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim 68167, Germany 20.Translational Lung Research Center Heidelberg (TRLC), German Center for Lung Research (DZL), Heidelberg 69120, Germany 21.German Cancer Consortium (DKTK), DKFZ, Core Center, Heidelberg 69120, Germany 22.Department of Pathology, Huashan Hospital, Fudan University, Shanghai 200040, China 23.These authors contributed equally 24.Lead contact
第一作者单位	免疫化学研究所; 生命科学与技术学院
通讯作者单位	免疫化学研究所
第一作者的第一单位	免疫化学研究所
推荐引用方式 GB/T 7714	Tianping Peng,Xiujian Ma,Wei Hua,et al. Individualized patient tumor organoids faithfully preserve human brain tumor ecosystems and predict patient response to therapy[J]. CELL STEM CELL,2025.
APA	Tianping Peng.,Xiujian Ma.,Wei Hua.,Changwen Wang.,Youjun Chu.,...&Ying Mao.(2025).Individualized patient tumor organoids faithfully preserve human brain tumor ecosystems and predict patient response to therapy.CELL STEM CELL.
MLA	Tianping Peng,et al."Individualized patient tumor organoids faithfully preserve human brain tumor ecosystems and predict patient response to therapy".CELL STEM CELL (2025).