| First Author | Consonni FM | Year | 2021 |
| Journal | Nat Immunol | Volume | 22 |
| Issue | 5 | Pages | 595-606 |
| PubMed ID | 33903766 | Mgi Jnum | J:305303 |
| Mgi Id | MGI:6706380 | Doi | 10.1038/s41590-021-00921-5 |
| Citation | Consonni FM, et al. (2021) Heme catabolism by tumor-associated macrophages controls metastasis formation. Nat Immunol 22(5):595-606 |
| abstractText | Although the pathological significance of tumor-associated macrophage (TAM) heterogeneity is still poorly understood, TAM reprogramming is viewed as a promising anticancer therapy. Here we show that a distinct subset of TAMs (F4/80(hi)CD115(hi)C3aR(hi)CD88(hi)), endowed with high rates of heme catabolism by the stress-responsive enzyme heme oxygenase-1 (HO-1), plays a critical role in shaping a prometastatic tumor microenvironment favoring immunosuppression, angiogenesis and epithelial-to-mesenchymal transition. This population originates from F4/80(+)HO-1(+) bone marrow (BM) precursors, accumulates in the blood of tumor bearers and preferentially localizes at the invasive margin through a mechanism dependent on the activation of Nrf2 and coordinated by the NF-kappaB1-CSF1R-C3aR axis. Inhibition of F4/80(+)HO-1(+) TAM recruitment or myeloid-specific deletion of HO-1 blocks metastasis formation and improves anticancer immunotherapy. Relative expression of HO-1 in peripheral monocyte subsets, as well as in tumor lesions, discriminates survival among metastatic melanoma patients. Overall, these results identify a distinct cancer-induced HO-1(+) myeloid subgroup as a new antimetastatic target and prognostic blood marker. |
