Serum LAG-3 Predicts Outcome and Treatment Response in Hepatocellular Carcinoma Patients With Transarterial Chemoembolization

Front Immunol. 2021 Oct 7:12:754961. doi: 10.3389/fimmu.2021.754961. eCollection 2021.

Abstract

Background: Transarterial chemoembolization (TACE) stands for the most commonly utilized therapy for hepatocellular carcinoma (HCC) worldwide. This study was to explore the potential predictive and prognostic roles of LAG-3 and PD-L1 as serum biomarkers in HCC patients underwent TACE treatment.

Methods: A total of 100 HCC patients receiving TACE as well as 30 healthy controls were enrolled in the study. Serum LAG-3 and PD-L1 levels were determined at baseline and 3 day after TACE using enzyme-linked immunosorbent assay (ELISA).

Results: We found serum levels of LAG-3 and PD-L1 were significantly elevated in HCC patients compared with healthy controls. Interestingly, patients with low pre-TACE and post-TACE levels of LAG-3 but not PD-L1 had a high probability of achieving an objective response (OR) after TACE treatment. Additionally, high pre-TACE LAG-3 level was correlated with poor disease outcome, and the patients with both high serum LAG-3 and PD-L1 level had the shorter overall survival (OS) than patients who are either PD-L1 or LAG-3 high or both PD-L1 and LAG-3 low. High pre-TACE serum LAG-3 level was positively associated with more cirrhosis pattern, advanced BCLC stage, pre-TACE alanine aminotransferase (ALT) level, and pre-TACE aspartate aminotransferase (AST) level. Furthermore, in 50 patients who underwent TACE, the serum LAG-3 level was significantly decreased at 3 day after TACE.

Conclusion: Both pre-TACE and post-TACE serum LAG-3 levels could serve as powerful predictors for tumor response of TACE, and high pre-TACE serum LAG-3 level was an indicator for poor prognosis in HCC.

Keywords: LAG-3; PD-L1; hepatocellular carcinoma; transarterial chemoembolization; tumor response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD / blood*
  • Biomarkers, Tumor / blood*
  • Carcinoma, Hepatocellular / blood*
  • Carcinoma, Hepatocellular / therapy*
  • Chemoembolization, Therapeutic
  • Female
  • Humans
  • Liver Neoplasms / blood*
  • Liver Neoplasms / therapy*
  • Lymphocyte Activation Gene 3 Protein
  • Male
  • Middle Aged
  • Prognosis
  • Treatment Outcome

Substances

  • Antigens, CD
  • Biomarkers, Tumor
  • Lymphocyte Activation Gene 3 Protein
  • Lag3 protein, human