The Prognostic Value of Circulating Stem Cells Expressing PD-L1 in Patients with Hepatocellular Carcinoma

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Background: Hepatocellular carcinoma (HCC) is associated with high recurrence rates despite curative-intent liver resection. This necessitates improved prognostic tools and novel therapeutic strategies, including immune checkpoint inhibitors (ICIs). Circulating stem cells (CSCs) have emerged as potential prognostic biomarkers. Aim: To assess the prognostic relevance of CSCs expressing programmed death-ligand 1 (PD-L1+CSCs) in relation to recurrence-free survival (RFS) and overall survival (OS) in patients undergoing surgery for HCC. Methods: PD-L1+CSCs (CD45-/CD146+/ASGPR+/CD90+/PD-L1+) were analyzed in 27 HCC patients before surgery, immediately after surgery, and at 6 and 12 months after surgery using fluorescence-activated cell sorting and immunofluorescence microscopy. Tumor recurrence was monitored biannually through alpha-fetoprotein (AFP) measurements and imaging (CT/MRI). Control groups included patients with benign liver disease, non-HCC malignancies, and healthy donors. Results: Before surgery, 29.7% (8/27) of HCC patients had detectable PD-L1+CSCs. Postoperatively, their frequency initially declined to 22.3%, followed by a significant rise to 85% at six months and 88% at twelve months (both p < 0.01). Increasing postoperative PD-L1+CSC levels were associated with tumor recurrence (51.8%). The presence of preoperative PD-L1+CSCs correlated with reduced OS (p = 0.05) and shorter RFS (p = 0.07). Conclusion: PD-L1+CSCs are associated with poor oncological outcomes and represent promising prognostic and therapeutic targets in HCC.

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