Heme oxygenase-1 orchestrates the immunosuppressive program of tumor-associated macrophages
| Autor: | Emmanuelle Alaluf, Stanislas Goriely, Aurélie Detavernier, Alice Carrette, Miguel P. Soares, Abdulkader Azouz, Louis Boon, Marion Splittgerber, Benoît Vokaer, Alain Le Moine, Frédérick Libert |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
medicine.medical_treatment T cell Immunology Cancer immunotherapy Biology CD8-Positive T-Lymphocytes 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Neoplasms Immunologie Tumor-Associated Macrophages medicine Immune Tolerance Tumor Microenvironment Animals Heme Innate immunity Mice Knockout Tumor microenvironment Innate immune system Macrophages Monocyte Membrane Proteins General Medicine Sciences bio-médicales et agricoles 3. Good health Heme oxygenase 030104 developmental biology medicine.anatomical_structure Oncology chemistry Tumor progression 030220 oncology & carcinogenesis Cancer research Heme Oxygenase-1 Research Article |
| Zdroj: | JCI Insight JCI insight, 5 (11 |
| ISSN: | 2379-3708 |
| DOI: | 10.1172/jci.insight.133929 |
| Popis: | Tumor-associated macrophages (TAMs) contribute to the maintenance of a strong immunosuppressive environment, supporting tumor progression and resistance to treatment. To date, the mechanisms that drive acquisition of these immunosuppressive features are still poorly defined. Heme oxygenase-1 (HO-1) is the rate-limiting enzyme that catabolizes free heme. It displays important cytoprotective, antiinflammatory, and antioxidant properties. A growing body of evidence suggests that HO-1 may also promote tumor development. Herein, we show that HO-1 is highly expressed in monocytic cells in the tumor microenvironment (TME) once they differentiate into TAMs. Deletion of HO-1 in the myeloid compartment enhances the beneficial effects of a therapeutic antitumor vaccine by restoring CD8+ T cell proliferation and cytotoxicity. We further show that induction of HO-1 plays a major role in monocyte education by tumor cells by modulating their transcriptional and epigenetic programs. These results identify HO-1 as a valuable therapeutic target to reprogram the TME and synergize with current cancer therapies to facilitate antitumor response. info:eu-repo/semantics/published |
| Databáze: | OpenAIRE |
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