Single-cell RNA landscape of intratumoral heterogeneity and immunosuppressive microenvironment in advanced osteosarcoma.

Tytuł:: Single-cell RNA landscape of intratumoral heterogeneity and immunosuppressive microenvironment in advanced osteosarcoma.
Autorzy:: Zhou Y; Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
Yang D; Orthopaedic Department of Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
Yang Q; Orthopaedic Department of Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
Lv X; Central Laboratory of the First Hospital of Nanchang, Nanchang, 330008, China.
Huang W; Pathology Department of Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
Zhou Z; Department of Orthopedic Oncology, Changzheng Hospital of Naval Military Medical University, Shanghai, 200003, China.
Wang Y; Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
Zhang Z; Orthopaedic Department of Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
Yuan T; Orthopaedic Department of Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
Ding X; Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
Tang L; Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
Zhang J; Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
Yin J; Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
Huang Y; Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
Yu W; Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
Wang Y; Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
Zhou C; Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
Su Y; Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
He A; Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
Sun Y; Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
Shen Z; Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
Qian B; MRC Centre for Reproductive Health & Edinburgh Cancer Research UK Centre, Queen's Medical Research Institute, EH16 4TJ, Edinburgh, United Kingdom.
Meng W; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.; Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Guangzhou, 510515, China.
Fei J; Department of Biochemistry and Molecular Biology, Medical College of Jinan University, 601 Western Huangpu Avenue, Guangzhou, 510632, China.
Yao Y; Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China. yangyao_.
Pan X; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China. .; Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Guangzhou, 510515, China. .
Chen P; Clinical Research Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201821, China. .
Hu H; Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China. .
Źródło:: Nature communications [Nat Commun] 2020 Dec 10; Vol. 11 (1), pp. 6322. Date of Electronic Publication: 2020 Dec 10.
Typ publikacji:: Journal Article; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Original Publication: [London] : Nature Pub. Group
MeSH Terms:: Genetic Heterogeneity*
Immunosuppression Therapy*
Single-Cell Analysis*
Osteosarcoma/*genetics
Osteosarcoma/*immunology
RNA, Neoplasm/*genetics
Tumor Microenvironment/*immunology
Adolescent ; Adult ; Cancer-Associated Fibroblasts/pathology ; Cell Aggregation/genetics ; Child ; Clone Cells ; DNA Copy Number Variations/genetics ; Dendritic Cells/pathology ; Female ; Humans ; Lymphocytes, Tumor-Infiltrating/immunology ; Macrophages/pathology ; Male ; Mesenchymal Stem Cells/pathology ; Myeloid Cells/pathology ; Neoplasm Staging ; Osteoclasts/metabolism ; Osteoclasts/pathology ; Osteosarcoma/pathology ; RNA, Neoplasm/metabolism ; Stromal Cells/pathology ; Transcriptome/genetics ; Young Adult
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Grant Information:: 17367 United Kingdom CRUK_ Cancer Research UK
Substance Nomenclature:: 0 (RNA, Neoplasm)
Entry Date(s):: Date Created: 20201211 Date Completed: 20201228 Latest Revision: 20240210
Update Code:: 20240210
PubMed Central ID:: PMC7730477
DOI:: 10.1038/s41467-020-20059-6
PMID:: 33303760
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Osteosarcoma is the most frequent primary bone tumor with poor prognosis. Through RNA-sequencing of 100,987 individual cells from 7 primary, 2 recurrent, and 2 lung metastatic osteosarcoma lesions, 11 major cell clusters are identified based on unbiased clustering of gene expression profiles and canonical markers. The transcriptomic properties, regulators and dynamics of osteosarcoma malignant cells together with their tumor microenvironment particularly stromal and immune cells are characterized. The transdifferentiation of malignant osteoblastic cells from malignant chondroblastic cells is revealed by analyses of inferred copy-number variation and trajectory. A proinflammatory FABP4 + macrophages infiltration is noticed in lung metastatic osteosarcoma lesions. Lower osteoclasts infiltration is observed in chondroblastic, recurrent and lung metastatic osteosarcoma lesions compared to primary osteoblastic osteosarcoma lesions. Importantly, TIGIT blockade enhances the cytotoxicity effects of the primary CD3 + T cells with high proportion of TIGIT + cells against osteosarcoma. These results present a single-cell atlas, explore intratumor heterogeneity, and provide potential therapeutic targets for osteosarcoma.

Erratum in: Nat Commun. 2021 Apr 30;12(1):2567. (PMID: 33931654)

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