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Abstract
BackgroundCTLA-4 is a well-studied immune checkpoint protein that negatively regulates T cell-mediated immune responses. However, the expression of CTLA-4 in glioma and the effects of CTLA-4 on prognosis in patients with glioma have not yet been examined.MethodsWe investigated the protein level of CTLA-4 in human glioma samples, extracted genetic and clinical data from 1024 glioma patients to characterize CTLA-4 expression and its relationship with immune functions in gliomas. R language was used for statistical analysis.ResultsHigher CTLA-4 expression was found in patients with higher grade, isocitrate dehydrogenase (IDH)-wild-type, and mesenchymal-molecular subtype gliomas than in patients with lower grade, IDH-mutant, and other molecular subtype gliomas. Further analysis showed that there was a strong positive correlation between CTLA-4 and the specific marker gene expression of immune cells, including CD8+ T cells, regulatory T cells, and macrophages in both databases, suggesting that higher CTLA-4 expression in the glioma microenvironment induced greater immune cell infiltration compared with that in gliomas with lower CTLA-4 expression. We further explored the associations between CTLA-4 and other immune-related molecules. Pearson correlation analysis showed that CTLA-4 was associated with PD-1, CD40, ICOS, CXCR3, CXCR6, CXCL12 and TIGIT. Patients with glioma with lower CTLA-4 expression exhibited significantly longer overall survival. Thus, these findings suggested that increased CTLA-4 expression conferred a worse outcome in glioma.ConclusionsIn summary, our findings revealed the expression patterns and clinical characteristics of CTLA-4 in glioma and may be helpful for expanding our understanding of antitumor immunotherapy in gliomas.
Highlights
cytotoxic T-lymphocyte antigen (CTLA)-4 is a well-studied immune checkpoint protein that negatively regulates T cell-mediated immune responses
Patients and samples We used formalin-fixed and paraffin-embedded (FFPE) glioma specimens to detect the expression of CTLA-4. 58 glioma specimens from adult patients who underwent neurosurgical resection of gliomas at the Department of Neurosurgery, Xiangya Hospital were included in the analysis
CTLA‐4 expression status in glioma We analyzed the expression of CTLA-4 in glioma according to World Health Organization (WHO) grade, isocitrate dehydrogenase (IDH) mutation status, and different subtypes in The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases
Summary
CTLA-4 is a well-studied immune checkpoint protein that negatively regulates T cell-mediated immune responses. As a well-studied immune checkpoint protein, CTLA-4 plays a crucial role in the tumor immunoreaction process. By blocking the interaction between CTLA-4 and its ligands expressed by antigen presenting cells, inhibitors of CTLA-4 can block the inhibitory immune signal and restore anticancer immune responses. Inhibitors of CTLA-4 have been shown to have remarkable success in clinical cancer immunotherapy in recent years. Current trials are evaluating the use of this antibody for additional oncological indications Another humanized anti-CTLA-4 antibody, tremelimumab, has been shown to elicit favorable responses in clinical trials against different tumor types. Combined with immune checkpoint inhibitors targeting PD-1/PD-L1, antibodies that block CTLA-4 may have applications as immunotherapies for the treatment of various malignancies, including glioma
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