22P - Extracellular vesicles as predictive biomarkers for chemoimmunotherapy in biliary tract cancer

Background

Biliary tract cancers (BTCs) are often diagnosed in advanced stage and characterized by a poor prognosis. Chemotherapy in combination with immunotherapy is currently the standard first-line treatment for patients with advanced disease, but its effectiveness remains limited, with response rates <30%. Thus, the identification of predictive factors is an unmet clinical need. Several studies have 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.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.