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Heme oxygenase-1 orchestrates the immunosuppressive program of tumor-associated macrophages
- Source :
- JCI Insight, JCI insight, 5 (11
- Publication Year :
- 2020
-
Abstract
- 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.<br />info:eu-repo/semantics/published
- Subjects :
- 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
Subjects
Details
- ISSN :
- 23793708
- Database :
- OpenAIRE
- Journal :
- JCI Insight
- Accession number :
- edsair.doi.dedup.....69abb3a78913df7e9233ec84dc4ea05b
- Full Text :
- https://doi.org/10.1172/jci.insight.133929