Advanced development of biomarkers for immunotherapy in hepatocellular carcinoma

Front Oncol. 2023 Jan 16:12:1091088. doi: 10.3389/fonc.2022.1091088. eCollection 2022.

Abstract

Hepatocellular carcinoma (HCC) is the most common liver cancer and one of the leading causes of cancer-related deaths in the world. Mono-immunotherapy and combination therapy with immune checkpoint inhibitors (ICIs) and multitargeted tyrosine kinase inhibitors (TKIs) or anti-vascular endothelial growth factor (anti-VEGF) inhibitors have become new standard therapies in advanced HCC (aHCC). However, the clinical benefit of these treatments is still limited. Thus, proper biomarkers which can predict treatment response to immunotherapy to maximize clinical benefit while sparing unnecessary toxicity are urgently needed. Contrary to other malignancies, up until now, no acknowledged biomarkers are available to predict resistance or response to immunotherapy for HCC patients. Furthermore, biomarkers, which are established in other cancer types, such as programmed death ligand 1 (PD-L1) expression and tumor mutational burden (TMB), have no stable predictive effect in HCC. Thus, plenty of research focusing on biomarkers for HCC is under exploration. In this review, we summarize the predictive and prognostic biomarkers as well as the potential predictive mechanism in order to guide future research direction for biomarker exploration and clinical treatment options in HCC.

Keywords: biomarker; combination therapy; hepatocellular carcinoma; immunotherapy; tumor immune microenvironment.

Publication types

  • Review

Grants and funding

This research was funded by the CAMS Innovation Fund for Medical Sciences (CIFMS, Grant No. 2021-I2M-1-066) and the Translational Research Project of Medical Oncology Key Foundation of Cancer Hospital Chinese Academy of Medical Sciences (CICAMS-MOTRP, Grant No. 2022005).