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

Abstract

BackgroundTransarterial 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.MethodsA 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).ResultsWe 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.ConclusionBoth 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.

Clinical significance of circulating biomarkers of immune checkpoint molecules with atezolizumab plus bevacizumab therapy in unresectable hepatocellular carcinoma

“…26 According to recent studies, high expression of LAG-3 in tumor tissue or serum indicates an unfavorable prognosis in several cancers, including non-small-cell lung carcinoma, melanoma 27 and HCC. 15 Based on the above, the high blood LAG-3 level in patients with HCC is thought to re ect the suppression of T cell activation and possible resistance to ATZ + BV treatment.…”

“…11,13 Furthermore, effective killing of cancer cells by an anticancer immune mechanism requires the initiation, progression and iterative expansion of a series of stepwise events, referred to as the "cancer immune cycle." 14 The immune-related molecules and cancer immune cycles, such as programmed cell death 1 ligand 1 (CD274), 5 lymphocyte-activation gene 3 (LAG-3), 15 chemokine (C-C motif) ligand 2 (CCL2), 16 CCL4, 16 CCL5, 16 chemokine (C-X-C motif) ligand 1 (CXCL1), 17 CXCL9, 9 CXCL10, 18 CXCL12, 19 CXCL13, 20 C-C motif chemokine receptor 5 (CCR5), 19 interferon gamma (IFNγ), 18 interleukin 6 (IL-6), 6 and IL-8, 18 have been reported to be secreted into the peripheral blood in HCC patients. Therefore, we analyzed the association between serum levels of the immunerelated molecules, CD274, LAG-3, CCL2, 4, 5, CXCL1, 9, 10, 12, 13, CX3CL1, CCR5, IFNγ and IL-6, 8, and objective response (OR) and prognosis with ATZ + BV treatment for HCC.…”

Comprehensive Metabolic Profiling and Genome-wide Analysis Reveal Therapeutic Modalities for Hepatocellular Carcinoma

“…We found that there was a higher density of PD-L1 + immune cells in tumor tissues of cluster 2, while no differences were observed in LAG-3 + and FGL-1 + cell densities between cluster 2 and other clusters. Previous studies reported that patients with high expression of PD-L1 and low expression of LAG-3/FGL1 had a better prognosis [ 39 ], explaining why cluster 2 had a higher survival. In the future, we will analyze more common immune checkpoints in HCCs to perfect our research results.…”

N7-Methylguanosine Genes Related Prognostic Biomarker in Hepatocellular Carcinoma

“…Therefore, immune checkpoint inhibitors targeting the above-mentioned molecules may be one of the novel therapeutic options for the treatment of HCC. LAG3 is also a predictor of tumor response following therapy for HCC ( Guo et al, 2021 ). We found that the immune-suppressive cytokines like IL10, IL4, TGFB1, TGFB2, and TGFB3 were significantly expressed in patients with high-risk scores.…”