PD-L2 Serves as a Potential Prognostic Biomarker That Correlates With Immune Infiltration and May Predict Therapeutic Sensitivity in Lower-Grade Gliomas

Abstract

Although patients with lower-grade gliomas (LGGs; grades II and III) have a relatively favorable prognosis, patients frequently relapse and tend to progress to higher-grade gliomas, leading to treatment resistance, poor survival, and ultimately treatment failure. However, until now, thorough research has not yet been reported on the relationship between PD-L2 and immune infiltration and therapeutic sensitivity to immunotherapy and TMZ-based chemotherapy of LGGs. In this study, we found that the expression of PD-L2 is upregulated in glioma, with high PD-L2 expression predicting a worse prognosis. Univariate and multivariate Cox regression analysis both indicated that PD-L2 represented an independent prognostic factor with high accuracy in survival prediction for LGGs. A nomogram comprising of age, grade, IDH mutation, and PD-L2 was established for predicting OS. Additionally, PD-L2 was found to be remarkably correlated with immune infiltration and some anti-tumor immune functions. The degree of PD-L2 expression was also found to be strongly related to the prediction of therapeutic sensitivity to immunotherapy and TMZ-based chemotherapy. Furthermore, immunohistochemistry demonstrated that PD-L2 and the macrophage biomarker CD68 were both increased in glioma, with PD-L2 expression having a strong positive connection with CD68 expression. Taken together, PD-L2 is a prognostic biomarker for LGGs patients that may provide novel insights into glioma individualized therapeutic strategies and guide effective immunotherapy and chemotherapy.