Altered IL-12 signaling pathways contribute to the deficient IFN-A production by T splenocytes from tumor-bearing mice

Marta Torroella-Kouri, Lynn M. Herbert, Giselle Perry, Diana M. Lopez

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

IFN-Á is a crucial cytokine produced by T and NK cells. Previous work from our laboratory has reported that in T cells of BALB/c mice bearing the D1-DMBA-3 mammary tumor, IFN-Á production is down-regulated, due to decreased expression of IL-12 by macrophages of tumor bearers. IL-12 is the main inducer of IFN-Á production in T and NK cells. To exert its function, IL-12 interacts with its receptor (IL-12R), activating a JAK/STAT signaling pathway. Our investigation suggests that there is also a deficiency in the response to IL-12 by T cells from tumor hosts. The present work reports the results of RT-PCR experiments in the study of the IL-12R expression on T cells from normal and tumor bearers. Data showed a deficient expression of the IL-12R'2 chain on T cells from tumor hosts. Gene expression arrays on IL-12-activated T cells from normal and tumor bearers confirmed the RT-PCR results, and also showed decreased expression of IL-18R in tumor bearers' T cells. Arrays also showed down-regulated expression of JAK2, STAT 1, 3, 4 and IRF-1. Finally, increased expression of SOCS 1,3,4,5 and 7, as well of Protein inhibitor of activated STATs (Pias) 1 and y was also observed in tumor bearers' T cells.

Original languageEnglish (US)
Pages (from-to)345-354
Number of pages10
JournalCancer Genomics and Proteomics
Volume1
Issue number5-6
StatePublished - Jan 1 2004

Keywords

  • Gene expression microarrays
  • IFN-Á
  • IL-12 receptor
  • Signal transduction
  • T cells
  • Tumor immunity
  • Tumor-bearing mice

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Cancer Research
  • Biochemistry

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