PD-L1 expression on circulating tumor cells can be a predictive biomarker to PD-1 inhibitors combined with radiotherapy and antiangiogenic therapy in advanced hepatocellular carcinoma

Aim: A programmed death 1 (PD-1) inhibitor coupled with radiotherapy and antiangiogenic therapy is a potential therapeutic strategy for advanced hepatocellular carcinoma (HCC). We aimed to determine if circulating tumor cells (CTCs) positive for programmed death-ligand 1 (PD-L1) could be employed as a predictive biomarker in HCC patients receiving triple therapy.

Methods: In this study, HCC patients received a PD-1 inhibitor in combination with intensity-modulated radiotherapy (IMRT) and antiangiogenic therapy. Following IMRT, the PD-1 inhibitor was administrated once every 3 weeks, while the antiangiogenic drug was given once a day. Treatment was continued until the disease progressed. Two mL of peripheral blood was collected at baseline, 1 month, and 3 months after treatment for CTC enrichment using the CytoSorter^® system with a CytoSorter™ CTC PD-L1 Kit (Watson Biotech., China).

Result: A total of 47 HCC patients receiving the triple therapy were enrolled in this study. Patients with < 2 PD-L1⁺ CTCs at baseline had a higher objective response rate (ORR) and longer overall survival (OS) than those with ≥ 2 PD-L1⁺ CTCs (56.5% vs. 16.7%, p = 0.007; not reach vs. 10.8 months, p = 0.001, respectively). The count of PD-L1⁺ CTCs was found to be an independent predictive biomarker of OS. Furthermore, the objective response was more likely to be achieved in patients with a dynamic decrease in PD-L1⁺ CTC counts at 1 month after treatment.

Conclusions: Our study demonstrated that PD-L1⁺ CTCs could be a predictive biomarker for HCC patients receiving PD-1 inhibitors in combination with IMRT and antiangiogenic therapy.