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Circulating PD-L1-positive exosomes predict TACE refractoriness and post-treatment metastasis in HCC
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DOI：10.1186/s40001-026-04914-8.png)
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Abstract
En 中文
Transarterial chemoembolization (TACE) is a standard therapy for intermediate-to-advanced hepatocellular carcinoma (HCC); however, a considerable proportion of patients exhibit refractoriness or early post-treatment metastasis. Circulating exosomal programmed death-ligand 1 (exoPD-L1) may reflect systemic tumor-immune interactions, yet its prognostic value in TACE outcomes remains unclear. We retrospectively analyzed 317 treatment-naïve HCC patients undergoing initial TACE. Plasma samples collected before and four weeks after TACE were used to isolate exosomes, and PD-L1 levels were quantified via enzyme-linked immunosorbent assay (ELISA). Associations between exoPD-L1 and TACE refractoriness or 12-month post-treatment metastasis were evaluated using logistic regression and receiver operating characteristic (ROC) curve analysis. Baseline exoPD-L1 levels were significantly higher in TACE-refractory patients compared with responders (182.5 vs. 155.8 pg/mL, P = 0.042) and were independently associated with TACE refractoriness (adjusted odds ratio (OR) = 1.03, 95% confidence interval (CI): 1.01–1.05, P = 0.002; area under the curve (AUC) = 0.783). Post-TACE increases in exoPD-L1 were observed in patients who developed early metastasis (225.9 vs. 115.9 pg/mL in non-metastatic patients, P < 0.01) and were independently associated with 12-month metastasis risk (adjusted OR = 1.01 per pg/mL increase, 95% CI 1.00–1.02, P = 0.004; AUC = 0.730). These findings suggest that circulating exoPD-L1 may have potential as a minimally invasive biomarker for predicting TACE refractoriness and early metastatic progression in HCC. Baseline exoPD-L1 could help identify patients who might benefit from closer monitoring or alternative therapeutic strategies, while post-TACE changes may provide additional prognostic information. Further prospective studies are warranted to confirm these observations and clarify their clinical utility.
Keywords:
Hepatocellular carcinoma
Transarterial chemoembolization
Exosomes
PD-L1
Refractoriness
Metastasis
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