Host STAT2/type I interferon axis controls tumor growth

Int J Cancer. 2015 Jan 1;136(1):117-26. doi: 10.1002/ijc.29004. Epub 2014 Jun 17.


The role of STAT2 in mediating the antigrowth effects of type I interferon (IFN) is well-documented in vitro. Yet evidence of IFN-activated STAT2 as having tumor suppressor function in vivo and participation in antitumor immunity is lacking. Here we show in a syngeneic tumor transplantation model that STAT2 reduces tumor growth. Stat2(-/-) mice formed larger tumors compared to wild type (WT) mice. IFN-β treatment of Stat2(-/-) mice did not cause tumor regression. Gene expression analysis revealed a small subset of immunomodulatory genes to be downregulated in tumors established in Stat2(-/-) mice. Additionally, we found tumor antigen cross-presentation by Stat2(-/-) dendritic cells to T cells to be impaired. Adoptive transfer of tumor antigen specific CD8(+) T cells primed by Stat2(-/-) dendritic cells into tumor-bearing Stat2(-/-) mice did not induce tumor regression with IFN-β intervention. We observed that an increase in the number of CD4(+) and CD8(+) T cells in the draining lymph nodes of IFN-β-treated tumor-bearing WT mice was absent in IFN-β treated Stat2(-/-) mice. Thus our study provides evidence for further evaluation of STAT2 function in cancer patients receiving type I IFN based immunotherapy.

Keywords: STAT1; STAT2; antitumor; cross-presentation; dendritic cell; interferon; melanoma.

Publication types

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

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Culture Media, Conditioned
  • Dendritic Cells
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic / immunology
  • Interferon-beta / pharmacology*
  • Lung Neoplasms / immunology
  • Lung Neoplasms / secondary*
  • Lung Neoplasms / therapy
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / pathology*
  • Melanoma, Experimental / therapy
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Neoplasm Transplantation
  • STAT1 Transcription Factor / metabolism
  • STAT2 Transcription Factor / physiology*
  • T-Lymphocytes / immunology
  • Tumor Burden / immunology*


  • Antineoplastic Agents
  • Culture Media, Conditioned
  • STAT1 Transcription Factor
  • STAT2 Transcription Factor
  • Stat1 protein, mouse
  • Stat2 protein, mouse
  • Interferon-beta