Blood-based biomarkers for immune-based therapy in advanced HCC: Promising but a long way to go

Abstract

The introduction of immune checkpoint inhibitors (ICIs) represents a key shift in the management strategy for patients with hepatocellular carcinoma (HCC). However, there is a paucity of predictive biomarkers that facilitate the identification of patients that would respond to ICI therapy. Although several researchers have attempted to resolve the issue, the data is insufficient to alter daily clinical practice. The use of minimally invasive procedures to obtain patient-derived specimen, such as using blood-based samples, is increasingly preferred. Circulating tumor DNA (ctDNA) can be isolated from the blood of cancer patients, and liquid biopsies can provide sufficient material to enable ongoing monitoring of HCC. This is particularly significant for patients for whom surgery is not indicated, including those with advanced HCC. In this review, we summarize the current state of understanding of blood-based biomarkers for ICI-based therapy in advanced HCC, which is promising despite there is still a long way to go.

Higher Number of Tumor-Infiltrating PD-L1+ Cells Is Related to Better Response to Multikinase Inhibitors in Hepatocellular Carcinoma

“…HCC development is associated with a progressive dysfunction of both the innate and adaptive immune systems. The resulting increase in regulatory components and immune suppressors contribute to the formation of an immunosuppressive tumor microenvironment (TME) [ 24 ]. Among these immune suppressors, M2-polarized TAMs are of particular importance in HCC.…”

Isolation and characterization of cancer-associated fibroblasts in the tumor microenvironment of hepatocellular carcinoma

“…Macrophages are typically divided into M1 phenotypes, which have anti-tumor functions and promote inflammation, and M2 phenotypes, which suppress inflammation and immune activity for the tumor progression in the TME of HCC. 12 The correlation between macrophages and CAFs may play a role in the immune function of macrophages.…”

“… 9 Cells with anti-tumor functions, such as M1 macrophages and CD8 + cytotoxic T cells, are inhibited by immune checkpoint molecules, such as programmed death-ligand 1, T-cell immunoglobulin, and mucin-domain containing-3, which are expressed in CAFs. 11 , 12 CAFs have a direct immunosuppressive effect on anti-tumor immune cells by activating immunosuppressive cells, such as regulatory T cells, M2 macrophages, and myeloid-derived suppressor cells. 13 , 14 …”

Peripheral blood-based cell signature indicates response to interstitial brachytherapy in primary liver cancer

“…thymidine kinase 1 and immune checkpoint inhibition) are becoming increasingly important alongside conventional chemotherapy to achieve recurrences rate as low as possible (Finn et al 2020 ). In order to allocate the most suitable therapeutic option to each patient, it is of great relevance to have reliable biomarkers allowing for response prediction (Sung et al 2022 ; Zhu et al 2022 ). Several biomarkers have been analyzed for locoregional therapies that could be indicative for therapy response (Tampaki et al 2015 ).…”