The post sepsis-induced expansion and enhanced function of regulatory T cells create an environment to potentiate tumor growth

Karen A. Cavassani, William F. Carson IV, Ana Paula Moreira, Haitao Wen, Matthew A. Schaller, Makoto Ishii, Dennis M. Lindell, Yali Dou, Nicholas W. Lukacs, Venkateshwar G. Keshamouni, Cory M. Hogaboam, Steven L. Kunkel

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70 Scopus citations

Abstract

One of the more insidious outcomes of patients who survive severe sepsis is profound immunosuppression. In this study, we addressed the hypothesis that post septic immune defects were due, in part, to the presence and/or expansion of regulatory T cells (Tregs). After recovery from severe sepsis, mice exhibited significantly higher numbers of Tregs, which exerted greater in vitro suppressive activity compared with controls. The expansion of Tregs was not limited to CD25+ cells, because Foxp3 expression was also detected in CD25- cells from post septic mice. This latter group exhibited a significant increase of chromatin remodeling at the Foxp3 promoter, because a marked increase in acetylation at H3K9 was associated with an increase in Foxp3 transcription. Post septic splenic dendritic cells promoted Treg conversion in vitro. Using a solid tumor model to explore the function of Tregs in an in vivo setting, we found post septic mice showed an increase in tumor growth compared with sham-treated mice with a syngeneic tumor model. This observation could mechanistically be related to the ability of post septic Tregs to impair the antitumor response mediated by CD8+ T cells. Together, these data show that the post septic immune system obstructs tumor immunosurveillance, in part, by augmented Treg expansion and function.

Original languageEnglish (US)
Pages (from-to)4403-4411
Number of pages9
JournalBlood
Volume115
Issue number22
DOIs
StatePublished - Jun 3 2010

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Cavassani, K. A., Carson IV, W. F., Moreira, A. P., Wen, H., Schaller, M. A., Ishii, M., Lindell, D. M., Dou, Y., Lukacs, N. W., Keshamouni, V. G., Hogaboam, C. M., & Kunkel, S. L. (2010). The post sepsis-induced expansion and enhanced function of regulatory T cells create an environment to potentiate tumor growth. Blood, 115(22), 4403-4411. https://doi.org/10.1182/blood-2009-09-241083