49P - Prognostic relevance of baseline exosome-delivered PD-1, PD-L1, pan-BTN3As and BTN3A1 in advanced cholangiocarcinoma patients: Can immune checkpoints act as a sentinel for predicting survival?

Background

Cholangiocarcinoma (CCA) is a group of rare and aggressive malignancies arising from the biliary tree. Due to its high heterogeneity, the clinical manifestations are atypical and diagnosis is often late, resulting in poor prognosis with a 5-year overall survival rate of only about 10%. Although immune checkpoints inhibitors (ICIs) have recently changed the treatment landscape of advanced CCA, the improvement in survival remains only a few weeks, suggesting the need to identify new prognostic biomarkers. In this context, the aim of our study was to investigate if baseline plasma exosomes-delivered immunomodulatory proteins may predict prognosis of patients with advanced CCA.

Methods

Exosomes were isolated from plasma of advanced CCA patients using exoEasy Maxi kit and characterized by transmission electronic microscopy, nanosight and western blot. Through specific ELISA tests we measured the exosomal concentrations of PD-L1, PD-1, butyrophilin sub-family 3A/CD277 receptor (BTN3A1), pan-BTN3As, butyrophilin sub-family 2 member A1 (BTN2A1), and B- and T-lymphocyte attenuator (BTLA) in 40 patients affected by advanced CCA, before starting first-line treatment with durvalumab and standard cytotoxic therapy. The Kaplan–Meier method was used to generate the survival curves, while univariate analysis was performed using Cox proportional hazard regression models.

Results

For each analyzed exosome-delivered biomarker, advanced CCA patients were discriminated based on long (≥ 6 months) versus short progression-free survival (PFS < 6 months). The concentration cut-offs, obtained by receiver operating characteristic (ROC) analysis, allowed to observe that a lower median PFS was associated with higher baseline levels of PD-L1 (> 0.32 ng/mL), PD-1 (> 2.28 ng/mL), BTN3A1 (> 4.45 ng/mL), pan-BTN3As (> 10.06 ng/mL), BTN2A1 (> 4.69 ng/mL) and BTLA (> 2.18 ng/mL).

Conclusions

Our results suggested that high-risk advanced CCA patients could be identified through determination of the plasma exosome-delivered PD-L1, PD-1, BTN3A1, pan-BTN3As, BTN2A1 and BTLA levels.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

SiciliAn MicronanOTecH Research and Innovation CEnter “SAMOTHRACE” (MUR, PNRR-M4C2, ECS_00000022), spoke 3: Università degli Studi di Palermo, “S2-COMMs - Micro and Nanotechnologies for Smart & Sustainable Communities”.

Funding

MUR, PNRR-M4C2, ECS_00000022.

Disclosure

All authors have declared no conflicts of interest.