Simultaneous Expression of PD-1 and PD-L1 in Peripheral and Central Immune Cells and Tumor Cells in the Benign and Malignant Salivary Gland Tumors Microenvironment.

Abstract

To investigate the differential expression of PD-1 and PD-L1 in salivary gland tumors (SGTs, malignant and benign subtypes) and determine their association with the clinicopathological characterization of the patients. The immunohistochemistry was used to examine PD-1 and PD-L1 expression in specimens from 83 patients with primary SGTs including salivary ductal carcinoma (SDC), adenoid cystic carcinoma (AdCC), acinic cell carcinoma (ACC), mucoepidermoid carcinoma (MEC), warthin's tumors (WT), poleomorphic adenoma (PA) and other subtypes. The expression of PD-1 in peripheral and central immune cells (ICs) of MEC, and peripheral ICs of ACC was significantly higher than those with AdCC (P = 0.02, P = 0.02, P = 0.03, respectively). Interestingly, the expression of PD-1 was also observed in peripheral and central malignant tumor cells (TCs), particularly in SDC and ACC. Despite no significant difference in PD-L1 expression of TCs among malignant subtypes, the peripheral and central ICs of ACC and MEC were revealed to express PDL-1 significantly more than those with AdCC (P < 0.05). WTs were rich in PD-1/PD-L1 expressing ICs. However, the tumor microenvironment of PA generally had low levels of PD-1/PD-L1 expression. In general, the expression of PD-1 in peripheral and central TCs was found to be significantly higher in malignant tumors than in benign ones (P = 0.002 and P = 0.003, respectively). The simultaneous presentation of PD-1 and PD-L1 in TCs and ICs of SGTs, their significant association with disease severity as well as the positive correlation between these immune checkpoints may suggest the therapeutic potential of anti-PD-1 and anti-PDL-1 combinational immunotherapy for SGTs.