Prognostic significance of PD-L2 expression in patients with oral squamous cell carcinoma—A comparison to the PD-L1 expression profile

Abstract

Background: Despite the observed association of increased PD-L1 expression in peripheral blood of oral squamous cell carcinoma (OSCC) patients with histomorphologic parameters, the role of the PD1 ligands—PD-L1 and PD-L2—is insufficiently understood. Aim of the study was to investigate whether the alterations of PD-L1 and PD-L2 expression in blood are associated with survival and could serve as immune monitoring parameter. Moreover, it should be analyzed if PD-L2 is differentially expressed in tissue and blood samples of OSCC patients compared to healthy controls and if there is an association of PD-L2 expression with histomorphologic and prognostic tumor parameters. Methods: PD-L2 mRNA expression was analyzed in tumors and healthy oral mucosa specimens and in corresponding peripheral blood samples of 48 OSCC patients and 26 healthy controls using RT-qPCR. A cutoff point (COP) was determined and a chi-square test (χ2 test) was carried out. Survival analysis of PD-L2 and previously reported PD-L1 expression data was performed using Kaplan-Meier analysis (Log-rank test). Results: PD-L2 expression in tissue samples was significantly (P < 0.001) higher in OSCC patients compared to healthy controls. A significant association of PD-L2 expression above the COP (positive) with malignancy was ascertained (P < 0.001). A significant (P = 0.01) association of previously reported PD-L1 expression rates in peripheral blood with survival could be shown. Conclusion: Peripheral blood PD-L1 expression might be a prognostic marker for OSCC patients and a possible parameter to monitor immune dysfunction in malign diseases. In the peripheral blood, PD-L1 might be more relevant for immune tolerance than PD-L2. Local PD-L2 expression in tissue samples might be useful as a diagnostic parameter for malignancy and could contribute to the immunosuppressive local microenvironment in OSCC.