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Clinical characterization and immunosuppressive regulation of CD161 (KLRB1) in glioma through 916 samples
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Clinical characterization and immunosuppressive regulation of CD161 (KLRB1) in glioma through 916 samples
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Journal Article
Clinical characterization and immunosuppressive regulation of CD161 (KLRB1) in glioma through 916 samples
2022
Overview
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. CD161 (KLRB1) is a clinical diagnostic marker predicting negative course of patients with gliomas. It plays prominent immune‐evading roles in glioma, and the expression of CD161 on CD8+ lymphocytes gradually increases during glioblastoma genesis.
Publisher
John Wiley & Sons, Inc,John Wiley and Sons Inc
Subject
/ Biomarkers, Tumor - genetics
/ CD161
/ Genes
/ Genomes
/ Genomics
/ glioma
/ Humans
/ Immune Checkpoint Inhibitors - immunology
/ Isocitrate Dehydrogenase - genetics
/ Lymphocytes, Tumor-Infiltrating - immunology
/ NK Cell Lectin-Like Receptor Subfamily B - genetics
/ NK Cell Lectin-Like Receptor Subfamily B - immunology
/ Original
/ Patients
/ Receptors, Antigen, T-Cell - immunology
/ T-Lymphocytes, Cytotoxic - immunology
/ Tumors
