ArticleScientific reports2020
Hepatocellular carcinoma-derived high mobility group box 1 triggers M2 macrophage polarization via a TLR2/NOX2/autophagy axis.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 81 citations in OpenAlex.
- HMGB1 Post-Translational Modifications in Epstein-Barr Virus-Associated Nasopharyngeal Carcinoma: Current Evidence, Emerging Mechanistic Concepts, and Unresolved Questions.International journal of molecular sciences · 2026Review
- Toll-like receptor 2 modulates age-associated insulitis and fibrotic remodeling of Langerhans islets.Immunity & ageing : I & A · 2026Article
- NADPH oxidases in immunometabolism and disease pathology: mechanistic networks, pollutant triggers, and therapeutic frontiers.Cellular & molecular immunology · 2026Review
- Role of PANoptosis in the development of gastric immunity and related gastric mucosal disease (Review).Molecular medicine reports · 2026Review
- Reprogramming macrophages to treat liver diseases.Hepatology (Baltimore, Md.) · 2026Review
- NF-κB signaling in hepatocellular carcinoma: Mechanisms of tumor progression, immune evasion, and therapeutic resistance.Translational oncology · 2026Review
- Autophagy-mediated Kupffer cell polarization in liver cirrhosis reversal: Mechanistic insights and therapeutic strategies.Liver research (Beijing, China) · 2026Review
- FBXO22 promotes hepatocellular carcinoma progression via paracrine myo‑inositol‑induced M2‑type polarization of macrophages.International journal of molecular medicine · 2026Article
- Lessons from neoadjuvant immunotherapy in melanoma: understanding antitumour immunity and tumour escape.Nature reviews. Immunology · 2026Review
- An IGF2BP2-MYBL2-HMGB2 Signaling Axis Promotes Macrophage Immune Evasion in Hepatocellular Carcinoma.Cancer communications (London, England) · 2026Article
- HMGB1 as Double-Edged Regulator of Cancer Therapy: Mechanistic Roles in Chemotherapy Resistance and Immunotherapy Response.OncoTargets and therapy · 2026Review
- From Defense to Disease: NADPH Oxidase in Cellular Function and Dysregulation.Journal of immunology research · 2026Review
- HMGB1: A Central Node in Cancer Therapy Resistance.International journal of molecular sciences · 2025Review
- Dualistic Roles of High Mobility Group Box 1 in Cancer and Inflammation.Cancer medicine · 2025Review
- Senescence‑associated IL‑33 secretion undermines sorafenib efficacy in hepatocellular carcinoma via immune evasion.Oncology reports · 2025Article
- HMGB1 as an emerging key modulator of bone remodeling: a narrative review.Stem cell research & therapy · 2025Review
- Targeting tumor-associated macrophages to overcome immune checkpoint inhibitor resistance in hepatocellular carcinoma.Journal of experimental & clinical cancer research : CR · 2025Review
- 6-Gingerol, an active compound of ginger, attenuates NASH-HCC progression by reprogramming tumor-associated macrophage via the NOX2/Src/MAPK signaling pathway.BMC complementary medicine and therapies · 2025Article
- A novel TLR4 accessory molecule drives hepatic oncogenesis through tumor-associated macrophages.Cancer letters · 2025Article
- Role of the AKT signaling pathway in regulating tumor-associated macrophage polarization and in the tumor microenvironment: A review.Medicine · 2025Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In many human cancers, including hepatocellular carcinoma (HCC), high density of infiltrating tumor-associated macrophages (TAM) is associated with poor prognosis. Most TAMs express a M2 phenotype subsequently supporting tumor growth. How tumor cells polarize these TAMs to a pro-tumor M2 phenotype is still poorly understood. Our previous studies have revealed that a Toll-like receptor 2 (TLR2)-dependent autophagy triggered by hepatoma-derived factors down-regulates NF-κB p65 and drives M2 macrophage differentiation. However, the underlying mechanisms and potential hepatoma-derived TLR2 ligands are not clear. Here, we provide evidence to reveal that NADPH oxidase 2 (NOX2)-dependent reactive oxygen species (ROS) generation is crucial for HCC-induced autophagy, NF-κB p65 down-regulation and M2 phenotype polarization in primary macrophages. This NOX2-generated ROS production in abolished in TLR2-deficient macrophages. HCC-derived or recombinant high-mobility group box 1 (HMGB1) is able to trigger this TLR2-mediated M2 macrophage polarization. Blockage of HMGB1 and ROS by inhibitors, ethyl pyruvate and N-acetylcysteine amide, respectively, significantly reduces both M2 macrophage accumulation and liver nodule formation in HCC-bearing mice. Our findings uncover a HMGB1/TLR2/NOX2/autophagy axis to trigger M2 macrophage polarization in HCC that can be considered as a novel therapeutic target for treating HCC.
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