ArticleJournal for immunotherapy of cancer2021
Extracellular HMGB1 blockade inhibits tumor growth through profoundly remodeling immune microenvironment and enhances checkpoint inhibitor-based immunotherapy.
Article in Journal for immunotherapy of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers, 1 of them a synthesis that pooled it.
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Who cites it
125 citing papers in PubMed, 1 synthesis or guideline pooled it, 161 citations in OpenAlex.
- [Research Advances on the Autophagy and Ferroptosis in the Development and Treatment of Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Pooled it
- 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
- Damage-Associated Molecular Patterns in Mesothelioma: Drivers of Inflammation and Therapeutic Targets.International journal of molecular sciences · 2026Review
- DAMPs, PAMPs, and Alarmins: From Mechanism to Therapy.MedComm · 2026Review
- Integrative analysis of HMGB3 in esophageal carcinoma: expression profile, prognostic significance, and immune microenvironment associations.Translational cancer research · 2026Article
- Revealing the Biological Effect of theJournal of the American Chemical Society · 2026Article
- Targeting the HMGB1-IL32 pathway to alleviate T cell exhaustion in epithelial ovarian cancer.GeroScience · 2026Article
- Article
- Context-dependent release of HMGB1: cell death mode, cell type and LPS stress drive monomer and heterocomplex formation.Molecular medicine (Cambridge, Mass.) · 2026Article
- DAMP signaling networks: from receptors to diverse pathophysiological functions.Journal of advanced research · 2026Review
- Programmed cell death in lung cancer: mechanisms, immune responses, and therapeutics.Apoptosis : an international journal on programmed cell death · 2026Review
- The redox-sensitive protein HMGB1: intracellular and extracellular roles.Experimental & molecular medicine · 2026Review
- Remodeling the tumor dormancy ecosystem to prevent recurrence and metastasis.Signal transduction and targeted therapy · 2026Review
- Pan-Cancer Landscape of the Novel Oxygen Sensor ADO and Its Potential Role in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2026Article
- The double-edged sword of SASP in breast cancer: from tumor suppression to progression and therapy resistance.Frontiers in oncology · 2026Review
- HMGB1 as Double-Edged Regulator of Cancer Therapy: Mechanistic Roles in Chemotherapy Resistance and Immunotherapy Response.OncoTargets and therapy · 2026Review
- Prognostic significance and regulatory role of ACOT7 in the tumor immune microenvironment of breast invasive ductal carcinoma: a multi-omics analysis.Frontiers in immunology · 2026Article
- Dual-Action Theranostic Nanoparticles Delivering Toll-Like Receptor 2 Inhibitors and Chemotherapy Target Breast Cancer Cells and the Tumor Microenvironment.International journal of nanomedicine · 2026Article
- Recent Advances in Antitumor Nanomedicine Based on Covalent Organic Frameworks.International journal of nanomedicine · 2026Review
- From immune desert to hot tumor: the tripartite synergy of tumor microenvironment-exosomes-immunogenic cell death in pioneering solutions.Frontiers in immunology · 2026Review
65 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHigh-mobility group box 1 (HMGB1) is a multifunctional redox-sensitive protein involved in various intracellular (eg, chromatin remodeling, transcription, autophagy) and extracellular (inflammation, autoimmunity) processes. Regarding its role in cancer development/progression, paradoxical results exist in the literature and it is still unclear whether HMGB1 mainly acts as an oncogene or a tumor suppressor.
methodsHMGB1 expression was first assessed in tissue specimens (n=359) of invasive breast, lung and cervical cancer and the two distinct staining patterns detected (nuclear vs cytoplasmic) were correlated to the secretion profile of malignant cells, patient outcomes and the presence of infiltrating immune cells within tumor microenvironment. Using several orthotopic, syngeneic mouse models of basal-like breast (4T1, 67NR and EpRas) or non-small cell lung (TC-1) cancer, the efficacy of several HMGB1 inhibitors alone and in combination with immune checkpoint blockade antibodies (anti-PD-1/PD-L1) was then investigated. Isolated from retrieved tumors, 14 immune cell (sub)populations as well as the activation status of antigen-presenting cells were extensively analyzed in each condition. Finally, the redox state of HMGB1 in tumor-extruded fluids and the influence of different forms (oxidized, reduced or disulfide) on both dendritic cell (DC) and plasmacytoid DC (pDC) activation were determined.
resultsAssociated with an unfavorable prognosis in human patients, we clearly demonstrated that targeting extracellular HMGB1 elicits a profound remodeling of tumor immune microenvironment for efficient cancer therapy. Indeed, without affecting the global number of (CD45
conclusionCollectively, we present evidence that extracellular HMGB1 blockade may complement first-generation cancer immunotherapies by remobilizing antitumor immune response.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.