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

Abstract

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.

Keywords:

• malignant salivary gland tumors
• PD-L1
• PD-L2
• CTLA-4
• tumor-infiltrating lymphocytes
• relapse-free survival

Acknowledgments

The biospecimens for this study were provided by the Korea University Guro Hospital of National Biobank, a member of the National Biobank of Korea.

The study was supported by a grant received by Dr Eun Joo Kang from Korea University, Seoul, Korea (K1422231).

Disclosure

The authors report no conflicts of interest in this work.