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 immunerelated 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.