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Aberrant expression of programmed death-1 (PD-1) receptor/PD-1 ligand (PD-L1) proteins alters human immunoresponse and promotes tumor development and progression. We assessed the expression status of PD-1 and PD-L1 in spinal chordoma tissue specimens and their association with clinicopathological characteristics of patients. Formalin-fixed paraffin-embedded tumor samples from 54 patients with spinal chordoma were collected for immunohistochemical analysis of PD-1 and PD-L1 expression. The association of the expression levels of PD-1 and PD-L1 with clinicopathological variables and survival data were statistically analyzed. Lymphocyte infiltrates were present in all 54 patient samples. Of 54 samples, 37 (68.5%) had both positive PD-1 and PD-L1 expression in tumor cell membrane. Moreover, 38 (70.4%) and 12 (22.2%) had positive PD-1 and PD-L1 expression in tumor-infiltrating lymphocytes (TILs), respectively. Tumors with positive PD-L1 expression were significantly associated with advanced stages of chordoma (p = 0.041) and TIL infiltration (p = 0.005), and had a borderline association with tumor grade (p = 0.051). However, positive tumor PD-L1 expression was not significantly associated with local recurrence-free survival (LRFS) or overall survival (OS). PD-1 expression in TILs was associated with poor LRFS (χ(2) = 10.051, p = 0.002, log-rank test). Multivariate analysis showed that PD-L1 expression only in TILs was an independent predictor for LRFS (HR = 0.298, 95% CI: 0.098-0.907, p = 0.033), and OS (HR = 0.188, 95% CI: 0.051-0.687, p = 0.011) in spinal chordoma patients. In conclusion, PD-L1 expression in TILs was an independent predictor for both LRFS and OS in spinal chordoma patients. Our findings suggest that the PD-1/PD-L1 pathway may be a novel therapeutic target for the immunotherapy of chordoma.

Altered expression or activity of human telomerase reverse transcriptase (hTERT) has been associated with human carcinogenesis. This study detected hTERT expression in spinal chordoma tissues and associated the level of hTERT expression with clinicopathological data and patient survival. Tissue samples from 54 patients and 20 controls were subjected to immunohistochemical analysis of hTERT protein levels. hTERT expression levels were then analyzed for associations with patient survival rates and clinicopathological parameters (such as age, gender, tumor size, location, tumor grade, tumor stage, muscle invasion, recurrence or not, type of resection, tumor hemorrhage, tumor necrosis, levels of tumor-infiltrating lymphocytes (TILs) and Ki-67 expression). hTERT expression was detected in all 54 spinal chordomas. Expression levels were weak in 7, moderate in 17 and strong in 30 spinal chordoma tissue samples. In contrast, hTERT was rarely expressed in nucleus pulposus tissues (20 samples). hTERT expression was significantly associated with the Ki-67-staining index (t = -6.616, p < 0.001), TIL levels (F = 5.27, p = 0.008) and tumor invasion of the surrounding muscle tissue (t = -4.49, p < 0.001). Kaplan-Meier curves indicated that high hTERT expression was significantly associated with poor local recurrence-free survival of patients (χ(2) = 19.07, p < 0.001 via the log-rank test), but not associated with overall patient survival. Multivariate analysis of local recurrence-free survival demonstrated that hTERT expression was an independent prognostic factor among spinal chordoma patients (HR = 1.013, 95% CI: 1.002-1.024, p = 0.016). High hTERT expression was associated with spinal chordoma growth, invasion and poor patient prognosis. Future studies will investigate the use of hTERT as a biomarker to predict patient prognosis and disease progression or as a potential spinal chordoma therapy target.