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

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, Wenxi Yu, Yonggang Wang, Chenliang Zhou, Yang Su, Aina He, Yuanjue Sun, Zan Shen, Binzhi Qian, Wei Meng, Jia Fei, Yang Yao (), Xinghua Pan (), Peizhan Chen () and Haiyan Hu ()
Additional contact information
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
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
Peizhan Chen: Shanghai Jiao Tong University School of Medicine
Haiyan Hu: Oncology Department of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital

Nature Communications, 2020, vol. 11, issue 1, 1-17

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-20059-6

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