Dynamic monitoring of serum soluble programmed cell death ligand 1 as a response predictor to chemotherapy in metastatic or recurrent gastrointestinal cancer

BACKGROUND: Biomarkers in serum may have important clinical implications for personalized medicine, including therapeutic guidance, and monitoring of recurrence. The role of programmed cell death ligand 1 (PD-L1) expression as a tumor biomarker remains controversial. In this study, we aimed at determining the changes of soluble PD-L1 (sPD-L1) during first-line chemotherapy and assessing the association with treatment response and progression-free survival (PFS) of patients with advanced gastrointestinal cancer. METHODS: Blood samples from 115 gastrointestinal cancer patients who have not received any previous systemic chemotherapy for recurrent or metastatic disease were collected at the time of diagnosis and each response evaluation. Serum of sPD-L1 expression was tested by enzyme-linked immunosorbent assay (ELISA). The associations between the baseline level of serum sPD-L1 and clinical-pathological characteristics and prognosis were analyzed. we further dynamically monitored the level change of serum sPD-L1 during treatment and analyzed its relationship with clinical-pathological characteristics, chemotherapy response and prognosis. RESULTS: Among 115 metastatic gastrointestinal patients, the median serum sPD-L1 level was 0.777 (range, <0.156–6.680) ng/mL. In most cases, changes in sPD-L1 level correlated with treatment response. Patients with values of serum sPD-L1 decreasing after chemotherapy had better tumor response and median PFS compared with patients with values increasing after chemotherapy (ORR, 88.3% vs. 54.0% P=0.000005 and PFS, not reached vs. 27 months, P=0.00026). D-values of sPD-L1 in patients with progressive disease (PD) were observed increasing from 0.406 to 1.097 ng/mL between pre- and post-chemotherapy, while in those with better tumor response D-values decreased from 1.153 to 0.791 ng/mL after chemotherapy compared with baseline. In the logistic regression analysis, the change of sPD-L1 levels in serum after chemotherapy were found to be a prognostic factor for treatment response and PFS in the multivariate analysis. CONCLUSIONS: These results showed for the first time that sPD-L1 in serum samples of patients with advanced gastrointestinal cancer were changed after chemotherapy and increased serum sPD-L1 levels were poor prognostic factors for both tumor response and PFS of patients. Dynamic monitoring of serum sPDL1 after treatment may be served as a potential predictor to treatment response in gastrointestinal cancer patients.