Long-term effect of liver resection on circulating stem cells expressing PD-L1 in patients with hepatocellular carcinoma – Pilot study

Background Liver resection remains the most effective and practical treatment for hepatocellular carcinoma (HCC) patients. However, HCC still has a high recurrence rate after curative treatments. Consequently, there currently remains an unmet need for research on adjuvant therapy such as immune checkpoint inhibitors (ICIs) after curative treatment for HCC. ICIs have been shown to be an evolving novel treatment option in certain advanced solid tumors and have been recently approved for inoperable, advanced, and metastatic HCC. Because circulating stem cells (CSCs) are more likely to initiate tumor growth than mature cancer cells, a high level of CSCs may be a hint for HCC recurrence.

Aim The aim of the study is to determine if the expression of PD-L1 on CSCs (PD-L1⁺CSCs) prior to and during 1-year post-surgery follow-up is related to recurrence free survival (RFS) and overall survival (OS).

Methods We evaluated the efficacy of pre- and post-surgery PD-L1⁺CSCs as biomarkers for resectable HCC. Fluorescence-activated cell sorting (FACS) was performed on 28 HCC patients who underwent surgery. Multicolor flow cytometry was used to detect the number of PD-L1⁺CSCs: CD45-/CD146+/ASGPR+/CD90+/CD274 (PD-L1)+. The patients were monitored by CT or MRI for recurrence every 6 months after surgery.

Results In our pilot study, PD-L1⁺CSC (31/ml) was detected in 28.5% of HCC patients (n=8/28, mean 0.81± 2.22) before surgery and the rate decreased to 21.4% (n=6/28, mean 0.13±0.34) at the same day after tumor resection. However, the detection rate increased significantly up to 85% (n=17/20, p<0.01, mean 2.31±2.60) six month later and to 88% (n=15/17, p<0.01, mean 1.41±1.58) twelve months after surgery. Fourteen (50%) patients had recurrence after a median follow-up period of 12 months. Patients with positive PD-L1⁺CSC counts before surgery tend to have significantly lower OS (p=0.05) and lower RFS (p=0.06) compared to patients with no detected PD-L1⁺CSC. Patients undergoing open surgery (n=24) tend to have lower RFS compared to patients undergoing laparoscopic surgery (n=4, p=0.07). No relationship between tumor size and PD-L1⁺CSC counts before surgery was determined. Additionally, tumor size did not predict the RFS or OS in the HCC patients (p=ns).

Conclusions PD-L1⁺CSCs could predict HCC recurrence with high accuracy after curative tumor resection. PD-L1⁺CSCs may be the target of an adjuvant ICI for preventing HCC recurrence.

Publikationsverlauf

Artikel online veröffentlicht:
19. August 2022