ArticleInternational journal of cancer2022
The immunosuppression pathway of tumor-associated macrophages is controlled by heme oxygenase-1 in glioblastoma patients.
Article in International journal of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 31 citations in OpenAlex.
- Pancreatic ductal adenocarcinoma: integrating molecular insights for targeted interventions.Signal transduction and targeted therapy · 2026Review
- From mechanism to clinic: a panoramic perspective on targeting HMOX1 to overcome drug resistance.Journal of cancer research and clinical oncology · 2026Review
- Ferroptosis and metabolic reprogramming in the immunosuppressive microenvironment of glioblastoma: emerging mechanisms and novel strategies.Frontiers in immunology · 2026Review
- Hot-yet-suppressed under PD-1 blockade: an RMP-NRF2-PD-L1 axis associated with a reduced proportional response in hepatocellular carcinoma.Frontiers in immunology · 2026Article
- Drug-loaded nanoparticles induce immunogenic cell death and efficiently target cells from glioblastoma patients.Nanomedicine (London, England) · 2025Article
- Biopsy location and tumor-associated macrophages in predicting malignant glioma recurrence using an in-silico model.NPJ systems biology and applications · 2025Article
- The multi-target mechanism of action of Selaginella doederleinii Hieron in the treatment of nasopharyngeal carcinoma: a network pharmacology and multi-omics analysis.Scientific reports · 2025Article
- Mapping TAM-tumor crosstalk in glioma via ligand-receptor multi-omics: mechanisms of immune evasion.Frontiers in immunology · 2025Review
- ZnPPIX-Loaded Nanoemulsions Reprogram Immunosuppressive Macrophages in Vitro: A Potential Strategy for Glioblastoma Microenvironment Modulation.International journal of nanomedicine · 2025Article
- Targeting glioma-associated microglia and macrophages: a new frontier in glioblastoma immunotherapy.Frontiers in immunology · 2025Review
- Ferroptosis-Related Transcriptional Level Changes and the Role of CIRBP in Glioblastoma Cells Ferroptosis.Biomedicines · 2024Article
- Inhibition of Heme Oxygenase 1 Suppresses Growth, Migration, and Invasion, and Regulates Tumor-Infiltrating CD8+ T Cells and in Uveal Melanoma.Investigative ophthalmology & visual science · 2024Article
- Glutamine Metabolism Heterogeneity in Glioblastoma Unveils an Innovative Combination Therapy Strategy.Journal of molecular neuroscience : MN · 2024Article
- Present and Future of Immunotherapy in Patients With Glioblastoma: Limitations and Opportunities.The oncologist · 2024Review
- Article
- Immunometabolism of ferroptosis in the tumor microenvironment.Frontiers in oncology · 2024Review
- Heme catabolism and heme oxygenase-1-expressing myeloid cells in pathophysiology.Frontiers in immunology · 2024Review
- Cytoprotective Role of Heme Oxygenase-1 in Cancer Chemoresistance: Focus on Antioxidant, Antiapoptotic, and Pro-Autophagy Properties.Antioxidants (Basel, Switzerland) · 2023Review
- Comparable safety profile between neuro-oncology procedures involving stereotactic needle biopsy (SNB) followed by laser interstitial thermal therapy (LITT) and LITT alone procedures.Journal of neuro-oncology · 2023Article
- Epigenetics and Metabolism Reprogramming Interplay into Glioblastoma: Novel Insights on Immunosuppressive Mechanisms.Antioxidants (Basel, Switzerland) · 2023Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The immunosuppressive tumor microenvironment (TME) in glioblastoma (GBM) is mainly driven by tumor-associated macrophages (TAMs). We explored whether their sustained iron metabolism and immunosuppressive activity were correlated, and whether blocking the central enzyme of the heme catabolism pathway, heme oxygenase-1 (HO-1), could reverse their tolerogenic activity. To this end, we investigated iron metabolism in bone marrow-derived macrophages (BMDMs) isolated from GBM specimens and in in vitro-derived macrophages (Mφ) from healthy donor (HD) blood monocytes. We found that HO-1 inhibition abrogated the immunosuppressive activity of both BMDMs and Mφ, and that immunosuppression requires both cell-to-cell contact and soluble factors, as HO-1 inhibition abolished IL-10 release, and significantly reduced STAT3 activation as well as PD-L1 expression. Interestingly, not only did HO-1 inhibition downregulate IDO1 and ARG-2 gene expression, but also reduced IDO1 enzymatic activity. Moreover, T cell activation status affected PD-L1 expression and IDO1 activity, which were upregulated in the presence of activated, but not resting, T cells. Our results highlight the crucial role of HO-1 in the immunosuppressive activity of macrophages in the GBM TME and demonstrate the feasibility of reprogramming them as an alternative therapeutic strategy for restoring immune surveillance.
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