期刊
CELL
卷 170, 期 1, 页码 127-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2017.06.016
关键词
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资金
- Dermatology Training Grant [5T32AR007098]
- DFCI Wong Family Award for Translational Cancer Research
- MSTP Grant [T32GM07739]
- MSTP Grant
- Beckman Young Investigator Program
- NIH New Innovator Award [DP2OD020839]
- Melanoma Research Alliance-BWH Department of Dermatology combined grant
- Cancer Research Institute
- Klarman Family Foundation
- National Institute of Arthritis and Musculoskeletal and Skin Disease [R01AR070234, K23 AR063461]
- Novartis
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. IFN gamma is necessary and sufficient to induce this program, revealing a key instructive role. Remarkably, homeostatic and IFN gamma-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 IFN gamma. 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.
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