Research Advance on Immune Microenvironment of Hepatocellular Carcinoma

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About this Research Topic

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Background

Hepatocellular carcinoma (HCC) occurs almost exclusively in the chronic inflammatory environment. This kind of inflammation often leads to the development of fibrosis/cirrhosis as the result of liver injury, tissue hyperplasia, and the activation of non-parenchymal cells, leading to chromosomal instability and the formation of the tumor microenvironment (TME) over time. The major cellular components of TME produce inflammatory cytokines, growth factors, extracellular matrix (ECM) proteins, etc., that influence HCC pathogenesis. Correspondingly, HCC pathogenesis causes the continuous high expression of proinflammatory cytokines that outstrips the anti-inflammatory reaction. The failure to maintain immune homeostasis contributes to liver fibrosis, cirrhosis, and eventual progression to HCC. Meanwhile, decreased CD4+ effector T cells, increased Treg cells, and T cell exhaustion due to the upregulation of KCs and elevated IL-10/TGF-β, contribute to T cell tolerance development. Decreased T-cell costimulatory factors associated with increased immune checkpoint molecules lead to T-cell effector dysfunction. Furthermore, there is growing evidence that intestinal permeability, microbiota, and microbial metabolites play an important role in HCC. The immune microenvironment promotes hepatocyte proliferation and provides them with a safe niche to escape immune surveillance. Therefore, strategies targeting the TME, especially the immune microenvironment, may be more effective in HCC treatment.

This Research Topic aims to shed light on the immune microenvironment of HCC in hepatocarcinogenesis, primary tumor growth, distant metastasis, potential targets, and treatment strategies. We welcome submissions covering but not limited to the following subtopics related to the immune microenvironment of HCC:

• Inflammation-involved immune exhaustion in HCC
• The intercellular crosstalk among HSCs, CAFs, endothelial cells, and immune cells in the immune microenvironment or immunotherapy of HCC
• Metabolic characterization of immune cells in the HCC immune microenvironment
• The potential of the gut-microbiota-liver axis in HCC clinical immunotherapy
• New strategies targeting the immune microenvironment to promote the efficacy of immunotherapy

Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.

Keywords: Tumor microenvironment, immune microenvironment, hepatocellular carcinoma, immunotherapy, immune tolerance

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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