The liver cancer immune microenvironment: Therapeutic implications for hepatocellular carcinoma

Abstract

The liver is the sixth most common site of primary cancer in humans and the fourth leading cause of cancer-related death in the world. Hepatocellular carcinoma (HCC) accounts for 90% of liver cancers. HCC is a prevalent disease with a progression that is modulated by the immune system. Half of the patients with HCC receive systemic therapies, traditionally sorafenib or lenvatinib, as a first-line therapy. In the last few years, immune-checkpoint inhibitors (ICIs) have revolutionized cancer therapy and have gained an increased interest in the treatment of HCC. In 2020, the combination of atezolizumab (anti-programmed death-ligand 1) and bevacizumab (antivascular endothelial growth factor) improved overall survival over sorafenib, resulting in Food and Drug Administration (FDA) approval as a first-line treatment for patients with advanced HCC. Despite these major advances, a better molecular and cellular characterization of the tumor microenvironment is still needed because it has a crucial role in the development and progression of HCC. Inflamed (hot) and noninflamed (cold) HCC tumors and genomic signatures have been associated with response to ICIs. However, there are no additional biomarkers to guide clinical decision-making. Other immune-targeting strategies, such as adoptive T-cell transfer, vaccination, and virotherapy, are currently under development. This review provides an overview on the HCC immune microenvironment, different cellular players, current available immunotherapies, and potential immunotherapy modalities.

A Novel Gene Signature Associated with Inflammatory Responses and Immune Status Assists in Prognosis and Intervention for Patients with HCC

“… 44–46 Previous study has determined that Anti-PD-L1, Anti- B7-1 (CD80) and B7-2 (CD86) checkpoint has been an innovative immunotherapeutic strategy. 47 , 48 In our study, we also found that expression levels of the PD-L1/2, B7-1 (CD80) and B7-2 (CD86) checkpoint molecules in the high-risk group were significantly increased compared with those in the low-risk group. This suggests that inhibition of these four immune checkpoint molecules can suppress the expression level of 7 gene signature, further inhibition of HCC progression.…”

Clinical neutrophil-associated genes as reliable predictors of hepatocellular carcinoma

“…In recent years, the clinical application of ICIs has increased the enthusiasm for HCC immunotherapy research. Studies showing that the combination of atezolizumab (anti-PD-L1) and bevacizumab (anti-VEGF) can significantly improve overall survival has made them first-line therapy for patients with advanced HCC ( Donisi et al, 2020 ; Donne and Lujambio, 2022 ; Sperandio et al, 2022 ). Besides ICI, there are other immunotherapy strategies under investigation, such as oncolytic virus immunotherapy and adoptive T cell transfer ( Foerster et al, 2022 ).…”

Identification of a nucleotide metabolism-related signature to predict prognosis and guide patient care in hepatocellular carcinoma

“…In the future, the risk score calculated by the model is expected to be a powerful complement to the clinical characteristics. Currently, the tumor immune microenvironment is a hot topic of research, and immune checkpoint inhibitors have been shown to be used for immunotherapy of tumors (Donne and Lujambio, 2022;Llovet et al, 2022). However, the prognosis of patients with hepatocellular carcinoma is hampered by the significant heterogeneity of patients and drug resistance after treatment (Cheng et al, 2020;Heinrich et al, 2021).…”