The Prognostic Value of Circulating Stem Cells Expressing PD-L1 in Patients with Hepatocellular Carcinoma
Dhruvajyoti Roy1, Elsie Oppermann2, Thomas J Vogl3
1Department of Breast Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
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.
