Tumor Microenvironment and Immune Modulation in Hepatocellular Carcinoma
Summary
The tumour microenvironment (TME) in hepatocellular carcinoma (HCC) comprises malignant hepatocytes, stromal cells, endothelial networks, extracellular matrix components and a heterogeneous infiltrate of immune cells. Throughout carcinogenesis, dynamic interactions between tumour cells and immune populations—particularly tumour-associated macrophages (TAMs), myeloid-derived suppressor cells and regulatory T lymphocytes—establish an immunosuppressive niche that fosters angiogenesis, invasion and metastatic spread. Conversely, antitumour effector populations such as M1-polarised macrophages, natural killer cells and cytotoxic T lymphocytes can be rendered dysfunctional by inhibitory cytokines, checkpoint ligand expression and metabolic reprogramming within the TME. Key signalling pathways including NF-κB, STAT, Wnt/β-catenin and bile-acid receptor cascades govern macrophage polarisation, fibroblast activation and vascular remodelling. Underlying liver disease, viral hepatitis or metabolic injury further shape antigen presentation and tolerance, influencing responsiveness to systemic therapies. Dissecting the molecular crosstalk that underpins immune suppression and tumour promotion has driven the rise of checkpoint inhibitors, targeted agents and combination regimens designed to reprogramme the TME toward immune activation and durable tumour control.
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Tumor Microenvironment and Immune Modulation in Hepatocellular Carcinoma publication trend
The graph below shows the total number of articles in tumor microenvironment and immune modulation in hepatocellular carcinoma across all publications each year (not limited to Nature Index journals).
Technical terms
Tumour Microenvironment (TME): The complex assembly of cancer cells, stromal elements, extracellular matrix and immune infiltrates that surrounds and influences a tumour.
Tumour-Associated Macrophages (TAMs): Macrophages residing within the TME that can adopt either an antitumour (M1) or a protumour (M2) phenotype.
M1/M2 Polarisation: Functional states of macrophages; M1 macrophages produce pro-inflammatory mediators and support antitumour immunity, whereas M2 macrophages secrete immunosuppressive factors and promote tumour growth.
Immune Checkpoint Inhibitor: A therapeutic antibody that blocks inhibitory receptors (such as PD-1) on T cells, unleashing antitumour immune responses.
Farnesoid X Receptor (FXR): A nuclear receptor that regulates bile-acid metabolism and influences immune cell behaviour in the liver.
References
- Blockage of CacyBP inhibits macrophage recruitment and improves anti-PD-1 therapy in hepatocellular carcinoma. Journal of Experimental & Clinical Cancer Research (2023).
- Immunosuppressive tumor microenvironment in the progression, metastasis, and therapy of hepatocellular carcinoma: from bench to bedside. Experimental Hematology & Oncology (2024).
- Role of ACSL4 in modulating farnesoid X receptor expression and M2 macrophage polarization in HBV‐induced hepatocellular carcinoma. MedComm (2024).
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