Biomarkers and prognostic factors of PD-1/PD-L1 inhibitor-based therapy in patients with advanced hepatocellular carcinoma

• Published in: Biomarker research Vol. 12; no. 1; p. 26
• Main Authors: Zhang, Nan, Yang, Xu, Piao, Mingjian, Xun, Ziyu, Wang, Yunchao, Ning, Cong, Zhang, Xinmu, Zhang, Longhao, Wang, Yanyu, Wang, Shanshan, Chao, Jiashuo, Lu, Zhenhui, Yang, Xiaobo, Wang, Hanping, Zhao, Haitao
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 14.02.2024; BioMed Central; BMC
• Subjects: Antigens; Apoptosis; B cells; Biological markers; Biomarker; Biomarkers; Biopsy; C-reactive protein; Cells; Clinical trials; Copy number; Cytokines; Dendritic cells; Development and progression; Extracellular matrix; Forecasts and trends; Gene expression; Genes; Hepatocellular carcinoma; Hepatoma; Immune checkpoint inhibitors; Immunotherapy; Intestinal microflora; Kinases; L-Lactate dehydrogenase; Liver; Liver cancer; Liver diseases; Lymphocytes; Macrophages; Medical prognosis; Medical research; Medicine, Experimental; Metabolomics; Metastases; Metastasis; Monoclonal antibodies; p53 Protein; Patients; PD-1 protein; PD-L1 protein; PET imaging; Prognosis; Programmed death ligand 1; Programmed death-1; Prothrombin; Response rates; Review; Spatial distribution; Thrombin; Tumor proteins; Tumor-infiltrating lymphocytes; Tumors; Vascular endothelial growth factor; Wnt protein; β-Catenin; France; Finland; Hepatocellular carcinoma; Biomarker; Immune checkpoint inhibitors; Programmed death ligand 1; Programmed death-1
• ISSN: 2050-7771; 2050-7771
• DOI: 10.1186/s40364-023-00535-z

Systemic therapies using programmed death-1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors have demonstrated commendable efficacy in some patients with advanced hepatocellular carcinoma (HCC); however, other individuals do not respond favorably. Hence, identifying the biomarkers, the prognostic factors, and their underlying mechanisms is crucial. In this review, we summarized the latest advancements in this field. Within the tumor microenvironment, PD-L1 expression is commonly utilized to predict response. Moreover, the characteristics of tumor-infiltrating lymphocytes are associated with the effectiveness of immunotherapy. Preclinical studies have identified stimulatory dendritic cells, conventional dendritic cells, and macrophages as potential biomarkers. The emergence of single-cell sequencing and spatial transcriptomics has provided invaluable insights into tumor heterogeneity through the lens of single-cell profiling and spatial distribution. With the widespread adoption of next-generation sequencing, certain genomic characteristics, including tumor mutational burden, copy number alterations, specific genes (TP53, CTNNB1, and GZMB), and signaling pathways (WNT/β-catenin) have been found to correlate with prognosis. Furthermore, clinical features such as tumor size, number, and metastasis status have demonstrated prognostic value. Notably, common indicators such as the Child-Pugh score and Eastern Cooperative Oncology Group score, which are used in patients with liver diseases, have shown potential. Similarly, commonly employed laboratory parameters such as baseline transforming growth factor beta, lactate dehydrogenase, dynamic changes in alpha-fetoprotein (AFP) and abnormal prothrombin, CRAFITY score (composed of C-reactive protein and AFP), and immune adverse events have been identified as predictive biomarkers. Novel imaging techniques such as EOB-MRI and PET/CT employing innovative tracers also have potential. Moreover, liquid biopsy has gained widespread use in biomarker studies owing to its non-invasive, convenient, and highly reproducible nature, as well as its dynamic monitoring capabilities. Research on the gut microbiome, including its composition, dynamic changes, and metabolomic analysis, has gained considerable attention. Efficient biomarker discovery relies on continuous updating of treatment strategies. Next, we summarized recent advancements in clinical research on HCC immunotherapy and provided an overview of ongoing clinical trials for contributing to the understanding and improvement of HCC immunotherapy.