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Cancer Immunology, Immunotherapy
Erschienen in:

27.01.2022 | Original Article

Single-cell transcriptome profiling reveals intra-tumoral heterogeneity in human chordomas

verfasst von: Wanru Duan, Boyan Zhang, Xinqiang Li, Wei Chen, Shanhang Jia, Zong Xin, Qiang Jian, Fengzeng Jian, Dean Chou, Zan Chen

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 9/2022

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Abstract

Chordoma is a rare and aggressive bone tumor. An accurate investigation of tumor heterogeneity is necessary for the development of effective therapeutic strategies. This study aims to assess the poorly understood tumor heterogeneity of chordomas and identify potential therapeutic targets. Single-cell RNA sequencing was performed to delineate the transcriptomic landscape of chordomas. Six tumor samples of chordomas were obtained, and 33,737 cells passed the quality control test and were analyzed. The main cellular populations identified with specific markers were as follows: chordoma cells (16,052 [47.6%]), fibroblasts (6945 [20.6%]), mononuclear phagocytes (4734 [14.0%]), and T/natural killer (NK) cells (3944 [11.7%]). Downstream analysis of each cell type was performed. Six subclusters of chordomas exhibited properties of an epithelial-like extracellular matrix, stem cells, and immunosuppressive activity. Although few immune checkpoints were detected on cytotoxic immune cells such as T and NK cells, a strong immunosuppressive effect was exerted on the Tregs and M2 macrophages. In addition, the cellular interactions were indicative of enhancement of the TGF-β signaling pathway being the main mechanism for tumor progression, invasion, and immunosuppression. These findings, especially from the analysis of molecular targeted therapy and tumor immune microenvironment, may help in the identification of therapeutic targets in chordomas.
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Metadaten
Titel
Single-cell transcriptome profiling reveals intra-tumoral heterogeneity in human chordomas
verfasst von
Wanru Duan
Boyan Zhang
Xinqiang Li
Wei Chen
Shanhang Jia
Zong Xin
Qiang Jian
Fengzeng Jian
Dean Chou
Zan Chen
Publikationsdatum
27.01.2022
Verlag
Springer Berlin Heidelberg
Erschienen in
Cancer Immunology, Immunotherapy / Ausgabe 9/2022
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-022-03152-1

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