Abstract
BackgroundImmune checkpoints like programmed cell death-1 (PD-1) and its ligand PD-L1 are involved in immune escape mechanisms of solid tumors including oral squamous cell carcinoma (OSCC). Inhibitors of the pathway are successfully used for treating especially advanced disease. However, the physiological relevance of PD-1/PD-L1-signaling in OSCC is insufficiently understood. The aim of the study was to analyze if PD-L1 expression in tumor tissue and peripheral blood samples of OSCC patients is associated with histomorphological tumor parameters and if PD-L1 expression in patients is different from controls.ResultsOSCC tumor specimens showed a significantly higher PD-L1 expression than oral mucosa controls (p < 0.001; upregulation more than 3-fold). Cross-tabulation revealed an association of increased expression of PD-L1 mRNA in tissue specimens with malignancy (p < 0.001).OSCC cases with higher tumor grade and cases with lymph node metastases (N+) were significantly (p < 0.05) associated with increased PD-L1 expression in peripheral blood. Cross-tabulation revealed an significant association with lymph node metastases (N+) (p ≤ 0.002).Materials and MethodsPD-L1 mRNA expression was analyzed in tumor specimens and corresponding samples of healthy oral mucosa and peripheral blood of 45 OSCC patients and 36 healthy control persons using RT-qPCR analysis. A Mann-Whitney U-test, a cut-off point analysis and a Chi-square test were carried out.ConclusionsPD-L1 expression in OSCC could contribute to the immunosuppressive local tumor microenvironment. Increased malignant behavior (higher tumor grade, positive nodal status) might be associated with PD-L1 mediated systemic immune tolerance. Thus, PD-L1 expression in peripheral blood might be an indicator of the existence of metastatic disease (N+) in OSCC.
Highlights
IntroductionOral squamous cell carcinomas (OSCC) are highly immunogenic tumors [2], an effective host defense reaction is not observed
There is emerging evidence that in addition to the biology of the tumor cell itself, the clinical course of malignant tumors is significantly influenced by the host immune response against cancer cells [1]. oral squamous cell carcinomas (OSCC) are highly immunogenic tumors [2], an effective host defense reaction is not observed
PD-L1 expression in peripheral blood might be an indicator of the existence of metastatic disease (N+) in OSCC
Summary
Oral squamous cell carcinomas (OSCC) are highly immunogenic tumors [2], an effective host defense reaction is not observed. New complementary “immune-scoring” systems including host derived immune response and immune tolerance towards the neoplastic disease are needed [5]. Immune tolerance is mediated by inhibitory signaling pathways, so called immune checkpoints. The programmed cell death-1 (PD-1) and the PD-1 ligand (PD-L1) pathway is one of the most relevant immunologic checkpoints [6], that is involved in the immune escape mechanism of solid tumors like OSCC. Immune checkpoints like programmed cell death-1 (PD-1) and its ligand PD-L1 are involved in immune escape mechanisms of solid tumors including oral squamous cell carcinoma (OSCC). The aim of the study was to analyze if PD-L1 expression in tumor tissue and peripheral blood samples of OSCC patients is associated with histomorphological tumor parameters and if PD-L1 expression in patients is different from controls
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