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

Ke Su; Lu Guo; Kun He; Mingyue Rao; Jianwen Zhang; Xiaoli Yang; Weihong Huang; Tao Gu; Ke Xu; Yanlin Liu; Jing Wang; Jiali Chen; Zhenying Wu; Lanxin Hu; Hao Zeng; Hongyan Li; Jian Tong; Xueting Li; Yue Yang; Hanlin Liu; Yaoyang Xu; Zunyuan Tan; Xue Tang; Xunjie Feng; Siyu Chen; Binbin Yang; Hongping Jin; Lechuan Zhu; Bo Li; Yunwei Han

doi:10.3389/fonc.2022.873830

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

Front Oncol. 2022 Aug 2:12:873830. doi: 10.3389/fonc.2022.873830. eCollection 2022.

Authors

Ke Su¹, Lu Guo², Kun He³, Mingyue Rao¹, Jianwen Zhang¹, Xiaoli Yang^{4

5

6}, Weihong Huang⁷, Tao Gu¹, Ke Xu¹, Yanlin Liu¹, Jing Wang³, Jiali Chen¹, Zhenying Wu¹, Lanxin Hu¹, Hao Zeng¹, Hongyan Li⁸, Jian Tong⁹, Xueting Li¹⁰, Yue Yang⁷, Hanlin Liu⁷, Yaoyang Xu⁷, Zunyuan Tan⁷, Xue Tang⁷, Xunjie Feng⁷, Siyu Chen⁷, Binbin Yang⁷, Hongping Jin⁷, Lechuan Zhu⁷, Bo Li^{4

5

6}, Yunwei Han^{1

5

6}

Affiliations

¹ Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
² Department of Ophthalmology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
³ Clinical Research Institute, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
⁴ Department of General Surgery (Hepatobiliary Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, China.
⁵ Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, China.
⁶ Academician (Expert) Workstation of Sichuan Province, Luzhou, China.
⁷ Clinical Medical College, Southwest Medical University, Luzhou, China.
⁸ Department of Anesthesiology, Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, China.
⁹ Department of Spinal Surgery, No.1 Orthopedics Hospital of Chengdu, Chengdu, China.
¹⁰ Department of Oncology, 363 Hospital, Chengdu, China.

Abstract

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.

Keywords: antiangiogenic therapy; circulating tumor cells; hepatocellular carcinoma; programmed death 1 inhibitor; programmed death-ligand 1; radiotherapy.