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Background/Aim: Cancer immune therapy by immune checkpoint inhibitors (ICIs) is a promising therapeutic strategy for various cancer types. Among ICIs, anti-programmed cell death protein-1 (PD1) and antiprogrammed death-ligand 1 (PD-L1) antibodies have shown a remarkable clinical benefit. The present study aimed to address the functional and clinical significance of serum levels of soluble PD-L1 (sPD-L1) in patients. Materials and Methods: A total of 21 patients, 11 with NSCLC, nine with gastric cancer and one with bladder cancer, who underwent anti-PD-1 therapy were evaluated for sPD-L1 concentration by ELISA analyses at diagnosis and after treatment. Results: Pretreatment levels of sPD-L1 in patients who received ICIs were not remarkably correlated with the overall survival of these patients (r=0.3394, p=0.1323). Reduction of plasma sPD-L1 level was significantly correlated with tumor regression in patients administered four cycles of treatment (p<0.05). Conclusion: sPD-L1 might be derived and secreted from tumors and might be useful to identify primary responders to ICIs at a relatively early treatment timepoint.Programmed death protein (PD1) and its ligand PD-L1 are central components in immune suppression, comprising the so-called 'immune checkpoint' (1, 2). Accumulating evidence revealed that the PD1/PD-L1 pathway is closely involved in resistance to antitumor immunity in multiple cancer types. Therefore, targeting immune checkpoints using immune checkpoint inhibitors (ICIs), such as those against PD1/PD-L1, has contributed to recent advances in cancer therapeutics (3, 4). However, many patients failed to respond or developed resistance after an initial response to ICIs. Predictive biomarkers for identifying potential responders to ICIs are currently under debate (5). Notably, several lines of evidence suggest a correlation between tumor PD-L1 expression and response to ICIs in variable malignancies including lung adenocarcinoma, melanoma, refractory Hodgkin's lymphoma, and other solid tumor types (6-10). Intriguingly, such correlation was reported for the expression level of membrane-bound PD-L1 (mPD-L1) on tumor tissues and plasma level of soluble PD-L1 (sPD-L1) in the blood of patients with cancer, highlighting the importance of their prognostic value. Several studies showed that high expression of sPD-L1 was associated with a poor prognosis in multiple types of malignant tumor. This suggests that sPD-L1 might be a predictive marker for low treatment responses to conventional chemotherapy and patients with high expression of sPD-L1 might be suitable for ICI therapy (11)(12)(13)(14)(15)(16)(17)(18)(19)(20). However, it remains unclear whether the plasma sPD-L1 level is derived from malignant tumors pre-existing in patients and reflects a potential response to ICIs. Here, we measured the plasma level of sPD-L1 collected from patients with non-small cell lung cancer (NSCLC) and those with gastric cancer who underwent anti-PD1 therapy and analyzed 5195