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Integrative single-cell transcriptome analysis reveals immune suppressive landscape in the anaplastic thyroid cancer

Cancer Gene Therapy volume 30, pages 1598–1609 (2023)Cite this article

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Abstract

The tumor immune microenvironment (TIME) in ATC is a complex and diverse ecosystem. It is essential to have a comprehensive understanding to improve cancer treatment and prognosis. However, TIME of ATC and the dynamic changes with PTC has not been revealed at the single-cell level. Here, we performed an integrative single-cell analysis of PTC and ATC primary tumor samples. We found that immunosuppressive cells and molecules dominated the TIME in ATC. Specifically, the level of infiltration of exhausted CD8+ T cells, and M2 macrophages was increased, and that of NK cells, B cells, and M1 macrophages was decreased. The cytotoxicity of CD8+ T cells, γδT cells, and NK cells was decreased, and immune checkpoint molecules, such as LAG3, PD1, HAVCR2, and TIGIT were highly expressed in ATC. Our findings contribute to the comprehension of TIME in both PTC and ATC, offering insights into the immunosuppressive factors specifically associated with ATC. Targeting these immunosuppressive factors may activate the anti-tumor immune response in ATC.

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Fig. 1: Overview of immune infiltrates in PTC and ATC with scRNA-seq.
Fig. 2: Characterization of T and NK cells.
Fig. 3: The exhausted molecular features of CD8, γδ T cells, and NK cells.
Fig. 4: mIHC detection was performed on tumor tissues from 8 ATC and 8 PTC cases, and 4 indicators were simultaneously detected, including LAG3, PD1, TIM3, and CD8.
Fig. 5: Characterization of B cells.
Fig. 6: Characterization of Myeloid cells.

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Data availability

All the single-cell and bulk RNA-sequencing data in this study are obtained from public datasets, which are available in the Gene Expression Omnibus (GEO) database.

Code availability

The codes generated during this study are available at the Github repository (https://github.com/fengchaobio/scRNA-seq_TIME_ATC).

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Acknowledgements

We thank Dr. Guangchun Han and Tai Yanhong for the helpful discussions and Qinghai Provincial People’s Hospital for providing pathological tissue samples.

Funding

This work was supported by the National Natural Science Foundation of China (grant no. 81572620) and Natural Science Foundation of Shandong Province (grant no. ZR2023MH370).

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  1. These authors contributed equally: Chao Feng, Yujia Tao.

Authors and Affiliations

  1. Department of Basic Medical Sciences, The 960th Hospital of PLA, 250031, Jinan, China

    Chao Feng, Yujia Tao, Chao Yu, Lirui Wang, Xiao Liu & Yuan Cao

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Contributions

Y.C. conceived this study. Y.C. and X.L. jointly supervised the study. C.F., Y.T., C.Y., L.W., and X.L. contributed to sample and information collection and data generation. Y.C. and C.F. supervised the bioinformatics data processing and analysis. C.F. performed bioinformatics data analysis. Y.T., C.Y., and L.W. assisted with data processing and analysis. X.L. and C.Y. performed IHC staining. Y.C., C.F., and X.L. wrote and revised the manuscript and all co-authors reviewed the manuscript.

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Correspondence to Xiao Liu or Yuan Cao.

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Feng, C., Tao, Y., Yu, C. et al. Integrative single-cell transcriptome analysis reveals immune suppressive landscape in the anaplastic thyroid cancer. Cancer Gene Ther 30, 1598–1609 (2023). https://doi.org/10.1038/s41417-023-00663-6

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