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Single-cell atlas reveals the immunosuppressive microenvironment and Treg cells landscapes in recurrent Glioblastoma

Cancer Gene Therapy (2024)Cite this article

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Abstract

Patients diagnosed with glioblastoma (GBM) have the most aggressive tumor progression and lethal recurrence. Research on the immune microenvironment landscape of tumor and cerebrospinal fluid (CSF) is limited. At the single-cell level, we aim to reveal the recurrent immune microenvironment of GBM and the potential CSF biomarkers and compare tumor locations. We collected four clinical samples from two patients: malignant samples from one recurrent GBM patient and non-malignant samples from a patient with brain tumor. We performed single-cell RNA sequencing (scRNA-seq) to reveal the immune landscape of recurrent GBM and CSF. T cells were enriched in the malignant tumors, while Treg cells were predominately found in malignant CSF, which indicated an inhibitory microenvironment in recurrent GBM. Moreover, macrophages and neutrophils were significantly enriched in malignant CSF. This indicates that they an important role in GBM progression. S100A9, extensively expressed in malignant CSF, is a promising biomarker for GBM diagnosis and recurrence. Our study reveals GBM’s recurrent immune microenvironment after chemoradiotherapy and compares malignant and non-malignant CSF samples. We provide novel targets and confirm the promise of liquid CSF biopsy for patients with GBM.

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Fig. 1: The landscape of recurrent malignant tumor samples and cerebrospinal fluid based on scRNA-seq.
Fig. 2: The transcriptional characteristics and differences between malignant samples.
Fig. 3: Survival and functional analysis based on S100A9 expression.
Fig. 4: Characterization of macrophage and T cells diversity in malignant microenvironment of GBM patients.
Fig. 5: Differences in immune microenvironment between malignant and non-malignant circumstance.
Fig. 6: Treg cells analyses in two CSF samples.

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Data availability

The expressional and survival validation data of S100A9 were downloaded from The Cancer Genome Atlas (TCGA, https://portal.gdc.cancer.gov/) and the Chinese Glioma Genome Atlas (CGGA, http://www.cgga.org.cn/) database. The scRNA-seq datasets generated during and analyzed during the current study have been uploaded in SRA with ID: PRJNA970244 and are available from Hengzhu Zhang and Yizhi Ge on reasonable request.

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Acknowledgements

We deeply acknowledged the great assistant from OE Biotech Co., Ltd. (Shanghai, China) and their technicist XiaoHua Yao. We also thank the data upload service from NCBI SRA Submissions.

Funding

This study was supported by the Postdoctoral Fund of the People’s Government of Jiangsu Province (200730000107) and the Postdoctoral Fund of Jiangsu Cancer Hospital (SZL202013).

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  1. These authors contributed equally: Xingdong Wang, Yizhi Ge, Yuting Hou.

Authors and Affiliations

  1. Department of Neurosurgery, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University/Clinical medical college, Yangzhou University, Yangzhou, Jiangsu, 225000, China

    Xingdong Wang, Xiaodong Wang, Zhengcun Yan, Yuping Li, Lun Dong, Lei She, Can Tang, Min Wei & Hengzhu Zhang

  2. Department of Radiation Oncology, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research and The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210009, China

    Yizhi Ge

  3. College of Medicine, Institute of Translational Medicine Yangzhou University, Yangzhou, Jiangsu, 225000, China

    Yuting Hou

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Contributions

All authors contributed to the study conception and design. Xingdong Wang, Yizhi Ge, and Yuting Hou were involved in the conceptualization, design, writing, and methodology of this study. Xiaodong Wang, Zhengcun Yan, and Yuping Li polish language. Lun Dong, Lei She, and Can Tang participated in the patients’ selection. Hengzhu Zhang and Min Wei performed conceptualization, design, data analysis, and critically revised the manuscript. All authors have read and approved the final version of the manuscript and consent to its publication.

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Correspondence to Min Wei or Hengzhu Zhang.

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Approval of the research protocol by an Institutional Reviewer Board: Subei People Hospital Institutional Review Board. Informed Consent: Informed consent was obtained from all patients. Registry and the Registration No. of the study/trial: N/A. Animal Studies: write N/A.

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Wang, X., Ge, Y., Hou, Y. et al. Single-cell atlas reveals the immunosuppressive microenvironment and Treg cells landscapes in recurrent Glioblastoma. Cancer Gene Ther (2024). https://doi.org/10.1038/s41417-024-00740-4

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