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

Author

Listed:
  • Yan Zhou

    (Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital)

  • Dong Yang

    (Orthopaedic Department of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital)

  • Qingcheng Yang

    (Orthopaedic Department of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital)

  • Xiaobin Lv

    (Central Laboratory of the First Hospital of Nanchang)

  • Wentao Huang

    (Pathology Department of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital)

  • Zhenhua Zhou

    (Changzheng Hospital of Naval Military Medical University)

  • Yaling Wang

    (Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital)

  • Zhichang Zhang

    (Orthopaedic Department of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital)

  • Ting Yuan

    (Orthopaedic Department of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital)

  • Xiaomin Ding

    (Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital)

  • Lina Tang

    (Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital)

  • Jianjun Zhang

    (Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital)

  • Junyi Yin

    (Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital)

  • Yujing Huang

    (Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital)

  • Wenxi Yu

    (Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital)

  • Yonggang Wang

    (Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital)

  • Chenliang Zhou

    (Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital)

  • Yang Su

    (Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital)

  • Aina He

    (Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital)

  • Yuanjue Sun

    (Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital)

  • Zan Shen

    (Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital)

  • Binzhi Qian

    (Queen’s Medical Research Institute)

  • Wei Meng

    (Southern Medical University
    Guangdong Provincial Key Laboratory of Single Cell Technology and Application)

  • Jia Fei

    (Medical College of Jinan University)

  • Yang Yao

    (Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital)

  • Xinghua Pan

    (Southern Medical University
    Guangdong Provincial Key Laboratory of Single Cell Technology and Application)

  • Peizhan Chen

    (Shanghai Jiao Tong University School of Medicine)

  • Haiyan Hu

    (Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital)

Abstract

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.

Suggested Citation

  • Yan Zhou & Dong Yang & Qingcheng Yang & Xiaobin Lv & Wentao Huang & Zhenhua Zhou & Yaling Wang & Zhichang Zhang & Ting Yuan & Xiaomin Ding & Lina Tang & Jianjun Zhang & Junyi Yin & Yujing Huang & Wenx, 2020. "Single-cell RNA landscape of intratumoral heterogeneity and immunosuppressive microenvironment in advanced osteosarcoma," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-20059-6
    DOI: 10.1038/s41467-020-20059-6
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    Cited by:

    1. Zenan Wang & Binghao Li & Shan Li & Wenlong Lin & Zhan Wang & Shengdong Wang & Weida Chen & Wei Shi & Tao Chen & Hao Zhou & Eloy Yinwang & Wenkan Zhang & Haochen Mou & Xupeng Chai & Jiahao Zhang & Zhi, 2022. "Metabolic control of CD47 expression through LAT2-mediated amino acid uptake promotes tumor immune evasion," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    2. Timothy I. Shaw & Jessica Wagner & Liqing Tian & Elizabeth Wickman & Suresh Poudel & Jian Wang & Robin Paul & Selene C. Koo & Meifen Lu & Heather Sheppard & Yiping Fan & Francis H. O’Neill & Ching C. , 2024. "Discovery of immunotherapy targets for pediatric solid and brain tumors by exon-level expression," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    3. Alexander Coulton & Jun Murai & Danwen Qian & Krupa Thakkar & Claire E. Lewis & Kevin Litchfield, 2024. "Using a pan-cancer atlas to investigate tumour associated macrophages as regulators of immunotherapy response," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    4. Nadège Gruel & Chloé Quignot & Laëtitia Lesage & Sophie El Zein & Sylvie Bonvalot & Dimitri Tzanis & Khadija Ait Rais & Fabien Quinquis & Bastien Manciot & Julien Vibert & Nadine El Tannir & Ahmed Dah, 2024. "Cellular origin and clonal evolution of human dedifferentiated liposarcoma," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    5. Yuki Matsushita & Jialin Liu & Angel Ka Yan Chu & Chiaki Tsutsumi-Arai & Mizuki Nagata & Yuki Arai & Wanida Ono & Kouhei Yamamoto & Thomas L. Saunders & Joshua D. Welch & Noriaki Ono, 2023. "Bone marrow endosteal stem cells dictate active osteogenesis and aggressive tumorigenesis," Nature Communications, Nature, vol. 14(1), pages 1-23, December.

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