The critical roles of lnc-GLYATL2-2/PD-L1 axis in immune microenvironment and the clinical value of intracranial chordomas

Intracranial chordomas (ICs) are associated with a poor prognosis due to low total resection rates and high recurrence rates. However, the role of immunotherapy in ICs remains unknown. RNA sequencing and immunohistochemical staining were performed on IC tissues and normal tissues, and the long noncoding RNA (lncRNA) lnc-GLYATL2-2 was identified. The results indicated that high expression of lnc-GLYATL2-2 was positively correlated with the tumor-infiltrating lymphocyte (TIL) markers CD4 and Foxp3, negatively correlated with CD8, and positively correlated with the expression of the immune checkpoint molecules programmed death receptor-1 (PD-1) and programmed death ligand 1 (PD-L1). Additionally, Kaplan-Meier and univariate or multivariate Cox regression analyses revealed the predictive value of lnc-GLYATL2-2 for survival based on clinical data from patients with ICs. A high expression level of lnc-GLYATL2-2 is potentially correlated with a suppressive tumor immune microenvironment and adverse clinical outcomes in IC patients. Mechanistically, the upregulation of lnc-GLYATL2-2 can result in increased cytoplasmic levels of ELAVL1, leading to enhanced binding to the 3'-UTR of PD-L1 mRNA and maintenance of its stability. In contrast, lnc-GLYATL2-2 can directly interact with the PD-L1 protein to prevent degradation, thereby promoting high levels of PD-L1 expression simultaneously at the transcriptional and translational levels in chordoma cells. These results provide a new perspective on the diagnosis and prognosis of ICs and provide theoretical evidence for immunotherapy in patients with ICs.