Prognostic significance of combined PD-L1 expression in malignant and infiltrating cells in hepatocellular carcinoma treated with atezolizumab and bevacizumab

Front Immunol. 2024 Dec 10:15:1506355. doi: 10.3389/fimmu.2024.1506355. eCollection 2024.

Abstract

Background: Programmed death-ligand 1 (PD-L1) expression is abundant not only in malignant cells but also in infiltrating cells within the tumor microenvironment (TME) of hepatocellular carcinoma (HCC). This study explored the association between PD-L1 expression in TME and outcomes in HCC patients treated with atezolizumab plus bevacizumab (AB), emphasizing the implications of PD-L1 expression in both malignant and tumor-infiltrating cells.

Methods: This study included 72 patients with HCC who underwent percutaneous core needle liver biopsy before AB treatment between September 2020 and December 2023. PD-L1 expression on tumor tissues was assessed using the combined positive score (CPS) with cutoff values of 1 and 10, utilizing antibody clone 22C3 (Dako).

Results: The distribution of PD-L1 CPS included 24 patients with CPS <1, 33 patients with CPS 1-10, and 15 patients with CPS ≥10. Significant differences in overall survival (OS) were observed across the three groups, with CPS ≥10 showing the highest survival rates (p = 0.010). Patients with CPS ≥10 had better OS than those with CPS <10 (median OS 14.8 vs. 8.3 months, P = 0.046), and CPS ≥1 had better OS than CPS <1 (P = 0.021). For progression-free survival (mPFS), the CPS ≥10 group had the highest median PFS of 11.0 months among the three groups (P = 0.044). Objective response rates (ORR) were higher in the PD-L1 CPS ≥10 group than in the 1-10 and <1 group (53.3%, 27.3%, and 16.7%, respectively; P = .047). Multivariate analysis identified that PD-L1 expression ≥10 and ≥1 were associated with favorable outcomes regarding OS (hazard ratio [HR] 0.283, P = .027 and HR 0.303, P = .006, respectively).

Conclusions: Combined analysis of PD-L1 expression in malignant and tumor-infiltrating cells can be a promising biomarker for the prognosis of HCC patients treated with AB.

Keywords: HCC; PD-L1; atezolizumab; objective response; overall survival.

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized* / administration & dosage
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • B7-H1 Antigen* / metabolism
  • Bevacizumab* / administration & dosage
  • Bevacizumab* / therapeutic use
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Hepatocellular* / drug therapy
  • Carcinoma, Hepatocellular* / immunology
  • Carcinoma, Hepatocellular* / metabolism
  • Carcinoma, Hepatocellular* / mortality
  • Carcinoma, Hepatocellular* / pathology
  • Female
  • Humans
  • Liver Neoplasms* / diagnosis
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / immunology
  • Liver Neoplasms* / metabolism
  • Liver Neoplasms* / mortality
  • Liver Neoplasms* / pathology
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Male
  • Middle Aged
  • Prognosis
  • Treatment Outcome
  • Tumor Microenvironment / immunology

Substances

  • atezolizumab
  • B7-H1 Antigen
  • Bevacizumab
  • Antibodies, Monoclonal, Humanized
  • CD274 protein, human
  • Biomarkers, Tumor

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The Basic Science Research Program supported this research through a National Research Foundation of Korea (NRF) funded by the Korean government (MSIT) (grant RS−2024−00337298). This research was also supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number RS-2024-00406716 to JH).