IFNγ-Dependent Tissue-Immune Homeostasis Is Co-opted in the Tumor Microenvironment. Academic Article uri icon

Overview

abstract

  • 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.

publication date

  • June 29, 2017

Research

keywords

  • Interferon-gamma
  • Melanoma
  • Monocytes
  • Neoplasm Metastasis
  • Skin Neoplasms
  • Suppressor of Cytokine Signaling Proteins
  • Tumor Microenvironment

Identity

PubMed Central ID

  • PMC5569303

Scopus Document Identifier

  • 85021662906

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2017.06.016

PubMed ID

  • 28666115

Additional Document Info

volume

  • 170

issue

  • 1