| First Author | Alaluf E | Year | 2020 |
| Journal | JCI Insight | Volume | 5 |
| Issue | 11 | PubMed ID | 32369450 |
| Mgi Jnum | J:341765 | Mgi Id | MGI:6717609 |
| Doi | 10.1172/jci.insight.133929 | Citation | Alaluf E, et al. (2020) Heme oxygenase-1 orchestrates the immunosuppressive program of tumor-associated macrophages. JCI Insight 5(11) |
| abstractText | 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. |
