6533b831fe1ef96bd1298cf3

RESEARCH PRODUCT

Prognostic significance of circulating PD-1, PD-L1, pan-BTN3As and BTN3A1 in patients with metastatic gastrointestinal stromal tumours (mGISTs)

subject

description

Abstract Background Gastrointestinal stromal tumours (GISTs) account for 1% of all primary gastrointestinal cancers. In cancer, suppressive immune checkpoints, including butyrophilin sub-family 3A/CD277 receptors (BTN3A), programmed death protein (PD-1) and its ligand PD-L1, are often hyper-activated to ensure an effective evasion of tumor cells from immune surveillance. Since recent studies showed that PD-1 and PD-L1 expression in cancer may be an important prognostic factor, the aim of our study was to investigate if soluble forms of inhibitory immune checkpoints can help predict survival in metastatic GIST patients. Methods Using specific homemade ELISA assays not yet commercially available, the plasma PD-1, PD-L1, BTN3A1 and pan-BTN3As levels were analyzed in 20 metastatic GIST patients harbouring c-KIT exon 11 mutations, before starting treatment with 400 mg Imatinib. Survival curves were estimated by using the Kaplan-Meier method and log-rank test to evaluate significant differences among them. Data was generated using the MedCalc software for Windows, version 18.2.1. Results Kaplan-Meier survival analysis was used to characterize prognostic relevance of soluble PD-1, PD-L1, BTN3A1 and pan-BTN3As in metastatic GIST patients, suggesting that their plasma levels could serve as survival predictor. For each analyzed biomarker, statistically significant differences in progression free-survival (PFS) between patients with plasma concentrations above and under median values were detected. Plasma level thresholds correlated with shorter survival and poor prognosis were established for PD-1 (>6.89 ng/ml), PD-L1 (>0.74 ng/ml), BTN3A1 (>7.19 ng/ml) and pan-BTN3As (>4.38 ng/ml). Conversely, patients with plasma levels under thresholds showed a median PFS that was approximately 58 months longer than to the previous. Conclusions Our study, for the first time, reveals that monitoring the concentration of soluble forms of inhibitory immune checkpoints in plasma can help predict survival in metastatic GIST patients and therefore improve their treatments. We showed that high plasma levels of these immune checkpoints correlate with poor outcome and could be used in future as prognostic factors. Legal entity responsible for the study The authors. Funding Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo. Disclosure All authors have declared no conflicts of interest.