The Prognostic Value of Plasma Programmed Death Protein-1 (PD-1) and Programmed Death-Ligand 1 (PD-L1) in Patients with Gastrointestinal Stromal Tumor

SIMPLE SUMMARY: No soluble biomarker is clinically implemented for patients with Gastrointestinal Stromal Tumor (GIST). High tissue expression of Programmed Death-Ligand 1 (PD-L1) has been associated with a poor prognosis in other cancer types. We aimed to investigate the prognostic value of plasma Programmed Death Protein-1 (PD-1)- and PD-L1 concentrations in patients with GIST. Sensitive immune-assays were used to determine the plasma PD-1 and PD-L1 concentrations in a national study, including 157 patients diagnosed with GIST, independent of disease- and treatment status. Patients with active GIST had significantly higher plasma concentrations of PD-1 and PD-L1 than patients without evidence of disease. Patients with active GIST had the highest plasma concentration of PD-L1 and a significantly poorer prognosis than patients with low concentrations of plasma PD-L1. ABSTRACT: Background: This study investigates the prognostic value of plasma Programmed Death Protein-1 (PD-1) and Programmed Death-Ligand 1 (PD-L1) concentrations in patients with Gastrointestinal Stromal Tumor (GIST). Methods: Patients with GIST were included (n = 157) from the two Danish sarcoma centers, independent of disease- and treatment status. The patients were divided into three subgroups; 1: patients with localized disease who underwent radical surgery; 2: patients with local, locally advanced, or metastatic disease; and 3: patients without measurable disease who had undergone radical surgery. Sensitive electrochemiluminescence immune-assays were used to determine PD-1 and PD-L1 concentration in plasma samples. The primary endpoint was the PFS. Results: No patients progressed in group 1 (n = 15), 34 progressed in group 2 (n = 122), and three progressed in group 3 (n = 20). Significantly higher plasma concentrations of PD-1 (p = 0.0023) and PD-L1 (0.012) were found in patients in group 2 compared to PD-1/PD-L1 levels in postoperative plasma samples from patient group 1. Patients with active GIST having a plasma concentration of PD-L1 above the cutoff (225 pg/mL) had a significantly poorer prognosis compared to patients with plasma PD-L1 concentration below the cutoff. Conclusions: Plasma PD-L1 shows potential as a prognostic biomarker in patients with GIST and should be further evaluated.