Cited by 684Sarcoma Diagnosis and TreatmentSingle-cell and spatial transcriptomicsBone Tumor Diagnosis and Treatments

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

Open access
Zhou, Yan, Yang, Dong, Yang, Qingcheng, Lv, Xiaobin, Huang, Wentao, Zhou, Zhenhua, Wang, Yaling, Zhang, Zhichang +20 more·2020·Nature Communications

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/s41467-020-20059-6

Cites

96 of 96 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Blocking TIGIT signaling significantly enhances the cytotoxicity of CD3+ T cells with high TIGIT expression against osteosarcoma cells.

    “Blocking TIGIT signaling can significantly enhance the cytotoxicity effects of CD3+ T cells with high expression of TIGIT against osteosarcoma cells, indicating potential therapeutic value of targeted TIGIT therapy for osteosarcoma [4].”

    From Advances on immunotherapy for osteosarcoma (2024) · cites this paper as [4]

    The Results (Heterogeneity of the TILs) report that TIGIT blockade significantly increased osteosarcoma-cell death in co-cultures with CD3+ T cells from patients BC3 and BC16, and the Discussion describes potential therapeutic value. Those patients had relatively high infiltration of TIGIT-positive CD3+ T cells in their tumors; the passage does not establish that the peripheral-blood CD3+ T cells used in the assay themselves had high TIGIT expression. (LLM, conf=0.82)

    Experimental — accuracy not yet measured
  • TIGIT is highly expressed by CD8+ T, CD4+ T, Treg and NKT cells in osteosarcoma lesions.

    “And the immunoreceptor inhibitory checkpoint marker TIGIT was highly expressed by the CD8+ T, CD4+ T, Treg and NKT cells in osteosarcoma lesions.”

    From Advances on immunotherapy for osteosarcoma (2024) · cites this paper as [4]

  • Targeted TIGIT therapy has potential therapeutic value for osteosarcoma.

    “indicating potential therapeutic value of targeted TIGIT therapy for osteosarcoma [4]”

    From Advances on immunotherapy for osteosarcoma (2024) · cites this paper as [4]

  • The seed and soil phenomenon in osteosarcoma is driven by a microenvironment that modulates osteosarcoma cell behaviour and facilitates proliferation, quiescence, invasion, migration and drug resistance, and contributes to intrinsic heterogeneity.

    “This seed and soil phenomenon is driven by a microenvironment that modulates osteosarcoma cell behaviour and facilitates proliferation, quiescence, invasion, migration, and drug resistance 15,51,52,53 and contributes to their intrinsic heterogeneity 54,55 .”

    From Osteosarcoma (2022) · cites this paper as [54]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Zhou, Y., Yang, D., Yang, Q., Lv, X., Huang, W., Zhou, Z., Wang, Y., Zhang, Z., Yuan, T., Ding, X., Tang, L., Zhang, J., Yin, J., Huang, Y., Yu, W., Wang, Y., Zhou, C., Su, Y., He, A., Sun, Y., Shen, Z., Qian, B., Meng, W., Fei, J., Yao, Y., Pan, X., Chen, P., & Hu, H.
Affiliations
  • Shanghai Jiao Tong University (CN)
  • Third Affiliated Hospital of Nanchang University (CN)
  • Second Military Medical University (CN)
  • Southern Medical University (CN)
  • Jinan University (CN)
  • Key Laboratory of Guangdong Province (CN)
Corresponding author
  • Yao, Yang
  • Pan, Xinghua
  • Chen, Peizhan
  • Hu, Haiyan
Venue
Nature Communications
Published
2020-12-10
Volume
11
Issue
1
Pages
6322-6322
ISSN
2041-1723 (ISSN-L)
OpenAlex
W3110998212
Cited by
672
References
96
Citations by year
2026: 106 · 2025: 136 · 2024: 152 · 2023: 139 · 2022: 96 · 2021: 41 · 2020: 2
FWCI
40.35
Type
journal article
Language
en
Open access
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (81372873, 8187215, 81503396, 81770173)
  • Please indicate the funder(s) of the research described in this manuscript, and the associated grant reference numbers
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
  • Health Sciences › Medicine › Rheumatology › Bone Tumor Diagnosis and Treatments
Keywords
osteosarcoma, intratumoral heterogeneity, tumor microenvironment, immunosuppression, single-cell transcriptomics, cell of origin, osteoblastic osteosarcoma, chondroblastic osteosarcoma, transdifferentiation, copy number variation, macrophage infiltration, FABP4, osteoclasts, lung metastasis, recurrent osteosarcoma, TIGIT, CD3+ T cells
MeSH terms
Cancer-Associated Fibroblasts, Adolescent, Adult, Cell Aggregation, Child, Clone Cells, Dendritic Cells, Female, Humans, Immunosuppression Therapy, Macrophages, Male, Neoplasm Staging, Osteoclasts, RNA, Neoplasm, Osteosarcoma, Lymphocytes, Tumor-Infiltrating, Stromal Cells, Genetic Heterogeneity, Myeloid Cells, Young Adult, DNA Copy Number Variations, Single-Cell Analysis, Tumor Microenvironment, Transcriptome, Mesenchymal Stem Cells

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review