2. Academic Validation
  3. Reconstruction of T cell infiltration in an osteosarcoma PDX-organoid interactive biobank for personalized immunotherapy

Reconstruction of T cell infiltration in an osteosarcoma PDX-organoid interactive biobank for personalized immunotherapy

  • Cell Rep Med. 2026 Mar 17;7(3):102644. doi: 10.1016/j.xcrm.2026.102644.
Wei Sun 1,  Yining Tao 2,  Xin He 1,  Qi Zhang 3,  Xiyu Yang 1,  Haoru Dong 1,  Haoyu Wang 1,  Weixi Chen 4,  Bing Yao 5,  Liyuan Zhang 6,  Winfred Mao 5,  Mingxi Li 5,  Yuqin Yang 7,  Zhengdong Cai 1,  Jinzeng Wang 8,  Haoran Mu 9,  Liu Yang 10,  Yingqi Hua 11
Affiliations

Affiliations

  • 1 Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Bone Tumor Institution, Shanghai, China.
  • 2 Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Bone Tumor Institution, Shanghai, China. Electronic address: [email protected].
  • 3 Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 4 SeekGene BioSciences Co., Ltd, Beijing, China.
  • 5 Apeiron Therapeutics, Shanghai, China.
  • 6 China Pharmaceutical University, Nanjing, China.
  • 7 Department of Laboratory Animal Center, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
  • 8 National Research Center for Translational Medicine at Shanghai, State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: [email protected].
  • 9 Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Bone Tumor Institution, Shanghai, China. Electronic address: [email protected].
  • 10 Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Bone Tumor Institution, Shanghai, China. Electronic address: [email protected].
  • 11 Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Bone Tumor Institution, Shanghai, China. Electronic address: [email protected].
PMID: 41763214 DOI: 10.1016/j.xcrm.2026.102644
Abstract

Osteosarcoma (OS) is an aggressive malignant bone tumor with limited therapeutic options and low response to immunotherapy. OS rarity slows clinical translation, highlighting the need for models that bridge patient-derived xenograft (PDX) systems and next-generation platforms. Here, we establish an OS PDX-organoid interactive biobank by self-assembling single-cell suspensions into individualized OS organoids (iOSs). iOS models recapitulate OS spatial and architectural features at millimeter scale in vitro and as xenografts and maintain functional pairing with matched PDX models. We validate iOS fidelity using histopathology, spatial features, genomics, transcriptomics, and pharmacogenomics. By reconstructing T cell infiltration in PDX-derived iOS models, we model treatment-associated immune responses and support immunotherapy translational studies. Using paired iOS-PDX models, we show that a PRMT5MTA inhibitor enhances immunotherapy response in chromosome 9p21.3-deleted OS.

Keywords

osteosarcoma, organoid, precision therapy, PRMT5.

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