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Patient-Derived Tumor Organoids Combined with Function-Associated ScRNA-Seq for Dissecting the Local Immune Response of Lung Cancer.
Liu, Chang; Li, Kaiyi; Sui, Xizhao; Zhao, Tian; Zhang, Ting; Chen, Zhongyao; Wu, Hainan; Li, Chao; Li, Hao; Yang, Fan; Liu, Zhidong; Lu, You-Yong; Wang, Jun; Chen, Xiaofang; Liu, Peng.
Afiliación
  • Liu C; School of Biomedical Engineering, Tsinghua University, Beijing, 100084, China.
  • Li K; School of Biomedical Engineering, Tsinghua University, Beijing, 100084, China.
  • Sui X; Department of Thoracic Surgery, People's Hospital, Peking University, Beijing, 100034, China.
  • Zhao T; School of Biomedical Engineering, Tsinghua University, Beijing, 100084, China.
  • Zhang T; Beijing Advanced Innovation Centre for Biomedical Engineering, Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100083, China.
  • Chen Z; School of Biomedical Engineering, Tsinghua University, Beijing, 100084, China.
  • Wu H; Beijing Advanced Innovation Centre for Biomedical Engineering, Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100083, China.
  • Li C; Department of Thoracic Surgery, People's Hospital, Peking University, Beijing, 100034, China.
  • Li H; Department of Thoracic Surgery, People's Hospital, Peking University, Beijing, 100034, China.
  • Yang F; Department of Thoracic Surgery, People's Hospital, Peking University, Beijing, 100034, China.
  • Liu Z; Beijing Chest Hospital, Capital Medical University & Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, 101125, China.
  • Lu YY; Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), School of Oncology, Beijing Cancer Hospital and Institute, Peking University, Beijing, 100142, China.
  • Wang J; Department of Thoracic Surgery, People's Hospital, Peking University, Beijing, 100034, China.
  • Chen X; Beijing Advanced Innovation Centre for Biomedical Engineering, Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100083, China.
  • Liu P; School of Biomedical Engineering, Tsinghua University, Beijing, 100084, China.
Adv Sci (Weinh) ; 11(31): e2400185, 2024 Aug.
Article en En | MEDLINE | ID: mdl-38896792
ABSTRACT
In vitro models coupled with multimodal approaches are needed to dissect the dynamic response of local tumor immune microenvironment (TIME) to immunotherapy. Here the patient-derived primary lung cancer organoids (pLCOs) are generated by isolating tumor cell clusters, including the infiltrated immune cells. A function-associated single-cell RNA sequencing (FascRNA-seq) platform allowing both phenotypic evaluation and scRNA-seq at single-organoid level is developed to dissect the TIME of individual pLCOs. The analysis of 171 individual pLCOs derived from seven patients reveals that pLCOs retain the TIME heterogeneity in the parenchyma of parental tumor tissues, providing models with identical genetic background but various TIME. Linking the scRNA-seq data of individual pLCOs with their responses to anti-PD-1 (αPD-1) immune checkpoint blockade (ICB) allows to confirm the central role of CD8+ T cells in anti-tumor immunity, to identify potential tumor-reactive T cells with a set of 10 genes, and to unravel the factors regulating T cell activity, including CD99 gene. In summary, the study constructs a joint phenotypic and transcriptomic FascRNA-seq platform to dissect the dynamic response of local TIME under ICB treatment, providing a promising approach to evaluate novel immunotherapies and to understand the underlying molecular mechanisms.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Organoides / Microambiente Tumoral / Neoplasias Pulmonares Límite: Humans Idioma: En Revista: Adv Sci (Weinh) Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Organoides / Microambiente Tumoral / Neoplasias Pulmonares Límite: Humans Idioma: En Revista: Adv Sci (Weinh) Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania