Inactivation of Interferon Receptor Promotes the Establishment of Immune Privileged Tumor Microenvironment

Cancer Cell. 2017 Feb 13;31(2):194-207. doi: 10.1016/j.ccell.2017.01.004.


Refractoriness of solid tumors, including colorectal cancers (CRCs), to immunotherapies is attributed to the immunosuppressive tumor microenvironment that protects malignant cells from cytotoxic T lymphocytes (CTLs). We found that downregulation of the type I interferon receptor chain IFNAR1 occurs in human CRC and mouse models of CRC. Downregulation of IFNAR1 in tumor stroma stimulated CRC development and growth, played a key role in formation of the immune-privileged niche, and predicted poor prognosis in human CRC patients. Genetic stabilization of IFNAR1 improved CTL survival and increased the efficacy of the chimeric antigen receptor T cell transfer and PD-1 inhibition. Likewise, pharmacologic stabilization of IFNAR1 suppressed tumor growth providing the rationale for upregulating IFNAR1 to improve anti-cancer therapies.

Keywords: IFNAR1; colorectal cancer; cytotoxic T cells; immunosuppression; interferon; receptor; tumor microenvironment.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Survival
  • Colorectal Neoplasms / etiology
  • Colorectal Neoplasms / immunology*
  • Colorectal Neoplasms / pathology
  • Down-Regulation
  • Humans
  • Immune Tolerance
  • Mice
  • Mice, Inbred C57BL
  • Receptor, Interferon alpha-beta / analysis
  • Receptor, Interferon alpha-beta / genetics
  • Receptor, Interferon alpha-beta / physiology*
  • Signal Transduction
  • T-Lymphocytes, Cytotoxic / physiology
  • Tumor Microenvironment


  • IFNAR1 protein, human
  • Receptor, Interferon alpha-beta