| First Author | Nirschl CJ | Year | 2017 |
| Journal | Cell | Volume | 170 |
| Issue | 1 | Pages | 127-141.e15 |
| PubMed ID | 28666115 | Mgi Jnum | J:243565 |
| Mgi Id | MGI:5909144 | Doi | 10.1016/j.cell.2017.06.016 |
| Citation | Nirschl CJ, et al. (2017) IFNgamma-Dependent Tissue-Immune Homeostasis Is Co-opted in the Tumor Microenvironment. Cell 170(1):127-141.e15 |
| abstractText | Homeostatic programs balance immune protection and self-tolerance. Such mechanisms likely impact autoimmunity and tumor formation, respectively. How homeostasis is maintained and impacts tumor surveillance is unknown. Here, we find that different immune mononuclear phagocytes share a conserved steady-state program during differentiation and entry into healthy tissue. IFNgamma is necessary and sufficient to induce this program, revealing a key instructive role. Remarkably, homeostatic and IFNgamma-dependent programs enrich across primary human tumors, including melanoma, and stratify survival. Single-cell RNA sequencing (RNA-seq) reveals enrichment of homeostatic modules in monocytes and DCs from human metastatic melanoma. Suppressor-of-cytokine-2 (SOCS2) protein, a conserved program transcript, is expressed by mononuclear phagocytes infiltrating primary melanoma and is induced by IFNgamma. SOCS2 limits adaptive anti-tumoral immunity and DC-based priming of T cells in vivo, indicating a critical regulatory role. These findings link immune homeostasis to key determinants of anti-tumoral immunity and escape, revealing co-opting of tissue-specific immune development in the tumor microenvironment. |
