Immune landscape and immunotherapy of hepatocellular carcinoma: focus on innate and adaptive immune cells

Abstract

Hepatocellular carcinoma (HCC) is responsible for roughly 90% of all cases of primary liver cancer, and the cases are on the rise. The treatment of advanced HCC is a serious challenge. Immune checkpoint inhibitor (ICI) therapy has marked a watershed moment in the history of HCC systemic treatment. Atezolizumab in combination with bevacizumab has been approved as a first-line treatment for advanced HCC since 2020; however, the combination therapy is only effective in a limited percentage of patients. Considering that the tumor immune microenvironment (TIME) has a great impact on immunotherapies for HCC, an in-depth understanding of the immune landscape in tumors and the current immunotherapeutic approaches is extremely necessary. We elaborate on the features, functions, and cross talk of the innate and adaptive immune cells in HCC and highlight the benefits and drawbacks of various immunotherapies for advanced HCC, as well as future projections. HCC consists of a heterogeneous group of cancers with distinct etiologies and immune microenvironments. Almost all the components of innate and adaptive immune cells in HCC have altered, showing a decreasing trend in the number of tumor suppressor cells and an increasing trend in the pro-cancer cells, and there is also cross talk between various cell types. Various immunotherapies for HCC have also shown promising efficacy and application prospect. There are multilayered interwoven webs among various immune cell types in HCC, and emerging evidence demonstrates the promising prospect of immunotherapeutic approaches for HCC.

Statin therapy: a potential adjuvant to immunotherapies in hepatocellular carcinoma

“…Chimeric antigen receptor (CAR)-T cells and T cell receptor (TCR) engineered T cells are 2 cell types of ACT therapy that are applied in the therapy of HCC. Currently, about 24 clinical trials related to CAR-T cell therapy for HCC are in phase I/II ( Gao and Zuo, 2023 ). Among these, glypican-3 (GPC3) is the main target.…”

“…Besides, an AFP-based vaccine has been designed for the treatment of AFP-positive HCC ( Lu et al, 2023 ). Recently, most of cancer vaccines were generated against HCC, such as the VEGF vaccine, the DC-based nano-vaccine, as well as a combination of vaccines and ICIs, and all applications have demonstrated the capacity to halt HCC progression ( Gao and Zuo, 2023 ; Lu et al, 2023 ). Virotherapy presents a novel immunotherapy modality for HCC.…”

New Mechanisms for Anti-Cancer Drugs

“…Frontiers in Pharmacology frontiersin.org 11 Wang et al 10.3389/fphar.2024.1324140 of cancer vaccines were generated against HCC, such as the VEGF vaccine, the DC-based nano-vaccine, as well as a combination of vaccines and ICIs, and all applications have demonstrated the capacity to halt HCC progression (Gao and Zuo, 2023;Lu et al, 2023). Virotherapy presents a novel immunotherapy modality for HCC.…”