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Updated: Oct 10, 2025
Isolation and Flow Cytometric Analysis of Glioma-infiltrating Peripheral Blood Mononuclear Cells
Published on: November 28, 2015
Clinical characterization and immunosuppressive regulation of CD161 (KLRB1) in glioma through 916 samples
Wang Di1, Wenhua Fan1, Fan Wu2
1Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Background:
Glioblastoma is a paradigm of cancer-associated immunosuppression, limiting the effects of immunotherapeutic strategies. Thus, identifying the molecular mechanisms underlying immune surveillance evasion is critical. Recently, the preferential expression of inhibitory natural killer (NK) cell receptor CD161 on glioma-infiltrating cytotoxic T cells was identified. Focusing on the molecularly annotated, large-scale clinical samples from different ethnic origins, the data presented here provide evidence of this immune modulator's essential roles in brain tumor biology.
Methods:
Retrospective RNA-seq data analysis was conducted in a cohort of 313 patients with glioma in the Chinese Glioma Genome Atlas (CGGA) database and 603 patients in The Cancer Genome Atlas (TCGA) database. In addition, single-cell sequencing data from seven surgical specimens of glioblastoma patients and a model in which patient-derived glioma stem cells were cocultured with peripheral lymphocytes, were used to analyze the molecular evolution process during gliomagenesis.
Results:
CD161 was enriched in high-grade gliomas and isocitrate dehydrogenase (IDH)-wildtype glioma. CD161 acted as a potential biomarker for the mesenchymal subtype of glioma and an independent prognostic factor for the overall survival (OS) of patients with glioma. In addition, CD161 played an essential role in inhibiting the cytotoxicity of T cells in glioma patients. During the process of gliomagenesis, the expression of CD161 on different lymphocytes dynamically evolved.
Conclusion:
The expression of CD161 was closely related to the pathology and molecular pathology of glioma. Meanwhile, CD161 promoted the progression and evolution of gliomas through its unique effect on T cell dysfunction. Thus, CD161 is a promising novel target for immunotherapeutic strategies in glioma treatment.
Insights
CD161, an inhibitory receptor on T cells, is highly expressed in glioblastoma, promoting tumor progression by impairing T cell function. Targeting CD161 offers a promising strategy for glioma immunotherapy.
Area of Science:
- Neuro-oncology
- Immunology
- Cancer Biology
Background:
- Glioblastoma exhibits significant immunosuppression, hindering immunotherapy efficacy.
- Understanding immune evasion mechanisms is crucial for effective brain tumor treatment.
- CD161, an inhibitory natural killer (NK) cell receptor, is preferentially expressed on glioma-infiltrating cytotoxic T cells.
Purpose of the Study:
- To investigate the role of CD161 in glioma pathology and its impact on anti-tumor immunity.
- To evaluate CD161 as a potential biomarker and therapeutic target in glioblastoma.
Main Methods:
- Retrospective analysis of RNA-seq data from 916 glioma patients (CGGA and TCGA databases).
- Single-cell sequencing of seven glioblastoma specimens.
- Co-culture model of patient-derived glioma stem cells and peripheral lymphocytes to study gliomagenesis.
Main Results:
- CD161 expression is enriched in high-grade, IDH-wildtype gliomas.
- CD161 serves as a biomarker for the mesenchymal subtype and an independent prognostic factor for overall survival.
- CD161 inhibits T cell cytotoxicity and its expression dynamically changes during gliomagenesis.
Conclusions:
- CD161 expression correlates with glioma pathology and molecular subtypes.
- CD161 promotes glioma progression by inducing T cell dysfunction.
- CD161 represents a promising therapeutic target for glioma immunotherapy.
