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Cancer Immunology, Immunotherapy

, Volume 60, Issue 7, pp 909–918 | Cite as

Prognostic role of FOXP3+ regulatory T cells infiltrating human carcinomas: the paradox of colorectal cancer

  • Sylvain Ladoire
  • François Martin
  • François Ghiringhelli
Review

Abstract

The accumulation of regulatory T cells (Tregs) at high density in various human carcinomas is generally associated with a poor prognosis, as expected from their capacity to inhibit antitumor immunity. Surprisingly, in patients bearing colorectal carcinoma (CRC), high regulatory T-cell infiltration is associated with a favorable prognosis, as shown by the analysis of seven clinical studies. To explain this paradox, we emphasize a putative role of the dense microbiological flora present in the large intestine with a trend toward translocation through the tumor. This microbiological hazard requires a T-cell-mediated inflammatory anti-microbial response that involves Th17 cells and can thereby promote cancer growth. This Th17-cell-dependent proinflammatory and tumor-enhancing response can be attenuated by Tregs, thus constituting a possible explanation for their favorable role in CRC prognosis. The link between a high density of FOXP3-positive cells in CRC immune infiltrates and favorable prognosis should lead us to consider tumor infiltrating Tregs as allies to be respected, rather than enemies to be destroyed during trials of CRC treatment.

Keywords

FOXP3 Regulatory T cells Colorectal cancer Prognosis Immune response 

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Sylvain Ladoire
    • 1
    • 2
  • François Martin
    • 1
  • François Ghiringhelli
    • 1
    • 2
    • 3
  1. 1.Institut National de la Santé et de la Recherche Médicale (INSERM). Avenir Team and CRI-866University of BurgundyDijonFrance
  2. 2.Department of Medical OncologyCentre de Lutte contre le Cancer Georges François LeclercDijonFrance
  3. 3.Centre Georges François Leclerc, Faculté de MédecineCentre de Recherche INSERM 866DijonFrance

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