PD-1 and PD-L1 interaction leads to immune evasion of various tumors and is associated with poor prognosis in patients with pancreatic cancer. Although immune check point inhibitor has yielded clinical benefits in several types of solid tumor, the efficacy was modest for pancreatic cancer. PD-L1 expressing exosomes can diminish immune responses against tumor, however, the roles of PD-L1 containing exosomes in pancreatic cancer are poorly understood.
Pre-treatment serum samples were collected from patients with advanced pancreatic cancer. Exosomes derived from the serum were isolated using Exoquick kit. Exosomal PD-L1 (exoPD-L1) was detected by enzyme-linked immuno-sorbent assay, and the concentration was further normalized to per milligram exosomal protein. PD-L1 expression in matched tissues were evaluated by PD-L1 immunohistochemistry (22C3) assay, described with combined positive score. Cutoff value of exoPD-L1 for survival was assessed with ROC curve analysis. Kaplan-Meier analysis was performed to obtain median overall survival.
In total, 77 samples of patients with advanced pancreatic cancer were analyzed for exoPD-L1 level. The median values of exoPD-L1 in plasma was 0.16 pg/mg (IQR, 0.12-0.20), and exoPD-L1 was not detected in 7 (9.0%) patients. ExoPD-L1 was measured significantly higher in patients with systemic disease than in locally advanced disease (p=0.023). Significant higher proportion of elevated exoPD-L1 was observed in patients with positive tissue PD-L1 expression versus those who were negative tissue PD-L1 expression (p=0.001). Patients were classified as two groups with low and high levels of exoPD-L1 using cutoff determined with ROC curves (0.165 pg/mg, AUC area 0.617, p=0.078). At a median follow-up of 7.97 months, the median OS was 11.2 months (95% CI, 6.33-16.1) in the low ExoPD-L1 group, as compared with 7.01 months (95% CI, 3.27-9.45) in the high ExoPD-L1 group (HR=0.65; 95% CI, 0.38-1.14; p=0.116).
The serum-derived exoPD-L1 levels were higher in metastatic pancreatic cancer than locally advanced disease. Patients with high exoPD-L1 levels tended to have a worse survival outcome than patients with low exoPD-L1 levels, though statistically not significant.
The authors.
Has not received any funding.
All authors have declared no conflicts of interest.