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

Abstract

ObjectivesPD-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 methodsWe 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.ResultsThe 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).ConclusionIn summary, PD-L2 is potentially an important biomarker in malignant salivary gland tumors, especially in regard to relapse.

The expression of programed death ligand‐1 could be related with unfavorable prognosis in salivary duct carcinoma

“…Although there have been some reports on the association between salivary gland carcinoma and PD‐L1 or PD‐L2, to the best of our knowledge, a few reports on PD‐L1/PD‐L2 in SDC have been found in the English literature . Mukaigawa et al examined the expression of PD‐L1 using 219 surgically resected salivary gland carcinomas.…”

“…When setting 1% as the cut‐off value of PD‐L1 expression, 15 cases (48%) had PD‐L1 expression and showed unfavorable prognosis. Chang et al investigated the expression of PD‐L1 and PD‐L2 using 70 surgically resected salivary gland carcinomas. Five (45%) and seven (64%) out of 11 cases showed high expression of PD‐L1 and PD‐L2, respectively.…”

“…To date, there has been no report on PD‐L2 expression in the non‐neoplastic epithelium of the salivary gland duct. PD‐L2 expression could be found in various salivary gland carcinomas compared to PD‐L1 . Regarding patient prognosis, Chang et al reported that low PD‐L2 expression in salivary gland tumors was associated with shorter relapse‐free survival.…”

“…PD‐L2 expression could be found in various salivary gland carcinomas compared to PD‐L1 . Regarding patient prognosis, Chang et al reported that low PD‐L2 expression in salivary gland tumors was associated with shorter relapse‐free survival. These findings indicate that PD‐L2 expression in a salivary gland carcinoma might be associated with tumor differentiation.…”

“…Programed death ligand 2 expression in various carcinomas seems to be correlated with impaired survival . On the other hand, positive PD‐L2 expression in metastatic melanoma is associated with improved overall survival .…”