CD48 is a key molecule of immunomodulation affecting prognosis in glioma

Cunyi Zou,1,* Chen Zhu,1,* Gefei Guan,1 Qing Guo,1 Tianqi Liu,1 Shuai Shen,1 Zihao Yan,1 Xiaoyan Xu,2 Zhiguo Lin,3 Ling Chen,4 Anhua Wu,1 Wen Cheng11Department of Neurosurgery, The First Hospital of China Medical University, Shenyang, Liaoning 110001, People’s Republic of China; 2Department of Pathophysiology, College of Basic Medicine Science, China Medical University, Shenyang, Liaoning 110122, People’s Republic of China; 3Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, People’s Republic of China; 4Department of Neurosurgery, General Hospital of People‘s Liberation Army of China (PLA), Medical College of PLA, Institute of Neurosurgery of PLA, Beijing 100853, People’s Republic of China *These authors contributed equally to thisworkPurpose: Glioma is a refractory disease associated with immune cell infiltration, and the effectiveness of checkpoint blockade remains suboptimal. As an adhesion and costimulatory molecule, CD48 plays a significant role in immunomodulation. As such, studying CD48 may provide additional understanding of the immune and inflammation response of glioma.Methods: Using R language and GraphPad Prism 7, RNA sequencing data of 946 patients from Chinese Glioma Genome Atlasand The Cancer Genome Atlas cohorts were analyzed.Results: CD48 was highly expressed in the malignant progression of glioma. As an independent risk factor, high-CD48 patients were associated with poor prognosis. CD48 influenced glioma purity and the local immune cell subpopulation. CD48 was closely related to immune function in glioma. Patients with an enhanced immune phenotype, high CD48, were associated with immune suppressive molecules and checkpoints. In addition, CD48 correlated with the immune and inflammatory response. A checkpoint risk score including CD48, SLAMF8 and PD-L1 was used to assess the role of checkpoints. Risk score was particularly high in a malignant subtype of glioma and was an independent predictive indicator of unfavorable outcome. Additionally, age, IDH subtype and MGMT promoter status influenced the predictive significance of checkpoint risk score.Conclusion: CD48 exhibits a crucial role in reduced survival and immunomodulation in glioma. In addition, we found that checkpoints play a greater role in patients older than 40 years old with IDH wild-type and MGMT methylated status. These findings suggest that combining CD48 blockade with PD-L1 may be a promising approach to glioma immunotherapy for specific subpopulations of patients.Keywords: CD48, glioma, prognosis, immunomodulation, immunotherapy