CTLA-4 correlates with immune and clinical characteristics of glioma

• Main Authors: Fangkun Liu, Jing Huang, Xuming Liu, Quan Cheng, Chengke Luo, Zhixiong Liu
• Format: Article
• Language: English
• Published: BMC 2020-01-01
• Series: Cancer Cell International
• Subjects: Immune checkpoint; CTLA-4; Immune response; Glioma; Prognosis
• Online Access: https://doi.org/10.1186/s12935-019-1085-6

Abstract Background CTLA-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. Methods We 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. Results Higher 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. Conclusions In 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.