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

Host STAT2/type I interferon axis controls tumor growth.

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  • 1Department of Biochemistry, Temple University School of Medicine, Philadelphia, PA.

Abstract

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.

© 2014 UICC.

KEYWORDS:

STAT1; STAT2; antitumor; cross-presentation; dendritic cell; interferon; melanoma

PMID:
24895110
[PubMed - indexed for MEDLINE]
PMCID:
PMC4199898
[Available on 2016-01-01]
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