IFN gamma-Dependent Tissue-Immune Homeostasis Is Co-opted in the Tumor Microenvironment

Cited 81 time in webofscience Cited 0 time in scopus
  • Hit : 48
  • Download : 0
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.
Publisher
CELL PRESS
Issue Date
2017-06
Language
English
Article Type
Article
Citation

CELL, v.170, no.1, pp.127 - +

ISSN
0092-8674
DOI
10.1016/j.cell.2017.06.016
URI
http://hdl.handle.net/10203/280419
Appears in Collection
BiS-Journal Papers(저널논문)
Files in This Item
There are no files associated with this item.
This item is cited by other documents in WoS
⊙ Detail Information in WoSⓡ Click to see webofscience_button
⊙ Cited 81 items in WoS Click to see citing articles in records_button

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0