Decreased accumulation of immune regulatory cells is correlated to the antitumor effect of IFN-ã overexpression in the tumor

Roberto Carrio, Marta Torroella-Kouri, Stephania Libreros, Ramón A. García-Areas, Vijaya Iragavarapu-Charyulu, Diana M. López

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

During mammary tumorigenesis, there is a profound tumor-induced immunosuppression and a progressive thymic atrophy associated with tumor development. IFN-γ has been shown to be effective in enhancing antitumor responses in several tumor models, however, how IFN-γ exerts its anti-tumor effect is largely controversial. In the present study we have used a mammary tumor model to investigate whether the levels of IFN-γ have an important role in the tumor-induced immunosuppression as well as in the pathogenesis of the thymic atrophy. We evaluated this possibility using DA-3 cells transfected to express IFN-γ (DA-3/IFN-γ), a system that provides constant, local production of IFN-γ within the tumor microenvironment. Overexpression of IFN-γ in the mammary tumor results in a marked delay of tumor growth, a reduction in regulatory T cells and myeloid-derived suppressor cells accumulation mostly due to down-regulation of chemokines implicated in the recruitment of immune regulatory cells, and a blockage in the tumor-associated thymus atrophy. Collectively, our data suggest that the replacement of the faulty levels of IFN-γ in the tumor results in a diminution of the tumor-induced immune suppression caused by the mammary tumor development.

Original languageEnglish (US)
Pages (from-to)1619-1627
Number of pages9
JournalInternational journal of oncology
Volume39
Issue number6
DOIs
StatePublished - Dec 2011

Keywords

  • IFN-γ
  • Myeloid-derived suppressor cells
  • Regulatory T cells
  • Tumor-bearing mice

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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