23P Non-small cell lung cancer DNA methylation profiles correlate with immune checkpoint inhibitor response

reported the use of liquid biopsy with the aim to identify circulating biomarkers with prognostic and predictive value.Extracellular vesicles (EVs), small particles secreted by cells that act as key mediators of intercellular communication, can be easily isolated from blood and have emerged as promising biomarkers for outcome prediction due to their role in cancer development and response to therapy.Methods: For the present study, we enrolled 17 patients with histological diagnosis of locally advanced or metastatic BTC that received first-line therapy with cisplatin + gemcitabine + durvalumab.A blood sample was collected before treatment start, and EVs were isolated from plasma by size-exclusion chromatography.EV enriched fractions were analyzed for size distribution and concentration using Nanosight NS300.EV surface proteins were analyzed by flow cytometry using the MACSPlex Exosome Kit human.Laboratory results were analysed in relation to clinical data, i.e. best treatment response.Results: Best treatment response was partial response (PR) for 4 patients, stable disease (SD) for 8, and progressive disease (PD) for 5 patients.No significant differences in terms of concentration and size distribution of EVs were reported among the 3 groups of patients.Thirteen EV surface epitopes were differentially expressed among the 3 groups.Interestingly, in PR compared to PD group, we report the overexpression of 6 markers correlated with immune cell activation (CD14, CD45), cell adhesion (CD49e), platelets and endothelial cells (CD142) and antigen presentation (HLA-ABC, HLA-DR). Conclusions:Our preliminary data show a potential role of EVs as predictive biomarker for treatment with chemoimmunotherapy in BTC.