Programmed death-ligand 1-expressing extracellular vesicles are a prognostic factor in patients with oral squamous cell carcinoma treated with immune checkpoint inhibitors

Abstract

Introduction

Immune checkpoint inhibitors (ICIs) have been clinically used to treat various cancers. This has resulted in a paradigm shift in the treatment of cancers, including recurrent/metastatic oral squamous cell carcinoma (R/M OSCC); however, response rate to treatment with ICIs is limited to 20–30%, and the treatment efficacy varies among patients. Therefore, developing a stratification method to accurately select patients expected to respond to the treatment would be beneficial. Extracellular vesicles (EVs) are important mediators of intercellular communication. Notably, programmed death-ligand 1 (PD-L1) is expressed on the surface of EVs in several malignancies. Herein, we focused on the clinical significance of PD-L1-expressing EVs (PD-L1 EVs) circulating in the serum of patients with R/M OSCC treated with ICIs.

Methods

Overall, 37 patients with R/M OSCC who were treated with ICIs at our institution were evaluated, and the optimum cutoff level of PD-L1 EVs was determined using a receiver operating characteristic analysis. Furthermore, we evaluated the association between PD-L1 EV levels and various clinicopathological features as well as the effects of PD-L1 EVs status on prognosis.

Results

The optimum cutoff level of PD-L1 EVs was 2.90 ng/mL. Further, Kaplan–Meier curve analysis revealed that high PD-L1 EV level was significantly associated with poor overall survival. Moreover, multivariate analysis indicated that high PD-L1 EV level was independently correlated with poor 5-year overall survival.

Conclusion

These findings indicate that assessing levels of PD-L1 EVs in serum before treatment may be a valuable prognostic indicator for patients with R/M OSCC following ICIs treatment.