@article{2536,
  keywords = {Animals, Mice, Humans, Cell Differentiation, Dendritic Cells, Sequence Analysis, RNA, Homeostasis, Neoplasm Metastasis, Transcriptome, Single-Cell Analysis, Skin Neoplasms, Melanoma, Tumor Microenvironment, Interferon-gamma, Monocytes, Suppressor of Cytokine Signaling Proteins},
  author = {Christopher Nirschl and Mayte Su{\'a}rez-Fari{\~n}as and Benjamin Izar and Sanjay Prakadan and Ruth Dannenfelser and Itay Tirosh and Yong Liu and Qian Zhu and Sanjana Devi and Shaina Carroll and David Chau and Melika Rezaee and Tae-Gyun Kim and Ruiqi Huang and Judilyn Fuentes-Duculan and George Song-Zhao and Nicholas Gulati and Michelle Lowes and Sandra King and Francisco Quintana and Young-suk Lee and James Krueger and Kavita Sarin and Charles Yoon and Levi Garraway and Aviv Regev and Alex Shalek and Olga Troyanskaya and Niroshana Anandasabapathy},
  title = {IFNγ-Dependent Tissue-Immune Homeostasis Is Co-opted in the Tumor Microenvironment.},
  abstract = {<p>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\&nbsp;immune mononuclear phagocytes share a conserved steady-state program during differentiation and entry into healthy tissue. IFNγ is necessary and sufficient to induce this program, revealing a key instructive role. Remarkably, homeostatic and IFNγ-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 IFNγ. SOCS2 limits adaptive anti-tumoral immunity and DC-based priming of T\&nbsp;cells in\&nbsp;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.</p>
},
  year = {2017},
  journal = {Cell},
  volume = {170},
  pages = {127-141.e15},
  month = {06/2017},
  issn = {1097-4172},
  doi = {10.1016/j.cell.2017.06.016},
  language = {eng},
}