PD-L2 expression is correlated with the molecular and clinical features of glioma, and acts as an unfavorable prognostic factor.

Background: Gliomas are aggressive tumors with various molecular and clinical characteristics and exhibit strongly resistance to radio-chemotherapy. Programmed cell death 1 ligand 2 (PD-L2) is a cell surface protein, which was reported in many cancers, modulating cancer-associated immune responses, while the role of PD-L2 in gliomas remained unclear. Herein, we aimed to investigate the biological behaviors and clinical prognostic values of PD-L2 in gliomas. Methods: Totally, we enrolled RNA sequencing data of 325 glioma samples from Chinese Glioma Genome Atlas (CGGA) as training cohort and RNA expression data of 1032 samples from The Cancer Genome Atlas (TCGA) dataset as validation cohort in this research. Then, the clinical and molecular characteristics, and the prognostic value of PD-L2 were analyzed. Results: We found that PD-L2 expression level was significantly upregulated in higher grade glioma and IDH wild-type glioma. Receiver Operating Characteristic (ROC) analysis revealed that PD-L2 was a potential indicator of mesenchymal subtype. PD-L2 exhibited tight relationship with immune response and immune-modulating process in glioma. Moreover, PD-L2 expression level could predict unfavorable prognoses of patients independent of age, grade, IDH status and 1p/19q status. Conclusions: Our study revealed that PD-L2 was closely related with inflammation and immune response. Patients with lower PD-L2 expression level tended to experience improved survival. Targeting PD-L2 may become a valuable approach for the treatment of gliomas in clinical practice.