Overexpression of PD-L2 is associated with shorter relapse-free survival in patients with malignant salivary gland tumors

Objectives: PD-1/PD-L1 and CTLA-4 have been investigated and are thought to play an important role in tumor evasion. This study aimed to investigate expression patterns of immune-related molecules, and their clinical impacts in malignant salivary gland tumors. Patients and methods: We performed immunohistochemical staining for PD-L1, PD-L2, CTLA-4, PD-1, and CD8⁺ tumor-infiltrating lymphocytes in 70 malignant salivary gland tumors. Protein expression was assessed by H-score by multiplying the staining intensity by the percentage of cells with positive staining. Results: The tumors comprised mucoepidermoid carcinomas (38.6%), adenoid cystic carcinomas (21.4%), salivary duct carcinomas (15.7%), and others. In malignant salivary gland tumors, PD-L2 expression was high, while expression of PD-L1 was relatively low in terms of the percentage of positively stained cells and the staining intensity. In univariate analysis, PD-L2 expression (H-score,1 vs ≥1), PD-1 (H-score,1 vs ≥1), and CD8⁺ tumor-infiltrating lymphocytes (H-score,1 vs ≥1) were significant prognostic factors. In multivariate analysis, low PD-L2 expression (H-score,1) was independently associated with shorter relapse-free survival (hazard ratio =6.514; 95% confidence interval, 1.2-36.2; P=0.032). Conclusion: In summary, PD-L2 is potentially an important biomarker in malignant salivary gland tumors, especially in regard to relapse.