Details

Autor(en) / Beteiligte

• Nirschl, Christopher J.
• Suárez-Fariñas, Mayte
• Izar, Benjamin
• Prakadan, Sanjay
• Dannenfelser, Ruth
• Tirosh, Itay
• Liu, Yong
• Zhu, Qian
• Devi, K. Sanjana P.
• Carroll, Shaina L.
• Chau, David
• Rezaee, Melika
• Kim, Tae-Gyun
• Huang, Ruiqi
• Fuentes-Duculan, Judilyn
• Song-Zhao, George X.
• Gulati, Nicholas
• Lowes, Michelle A.
• King, Sandra L.
• Quintana, Francisco J.
• Lee, Young-suk
• Krueger, James G.
• Sarin, Kavita Y.
• Yoon, Charles H.
• Garraway, Levi
• Regev, Aviv
• Shalek, Alex K.
• Troyanskaya, Olga
• Anandasabapathy, Niroshana

Titel

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

Ist Teil von

• Cell, 2017-06, Vol.170 (1), p.127-141.e15

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2017

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. 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 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. [Display omitted] •Immune phagocytes share a conserved program during differentiation and tissue entry•IFNγ is a critical instructive cue in the steady state•IFNγ and tissue programming are co-opted across cancers and include SOCS2•SOCS2 is a critical determinant of tumor-immune surveillance in dendritic cells Tumors exploit physiological mechanisms that are in place to keep tissue homeostasis in order to escape the surveillance of the immune system.