Article Text

Download PDFPDF
Identification of CD8+CD25+Foxp3+ suppressive T cells in colorectal cancer tissue
  1. N Chaput1,2,3,
  2. S Louafi1,2,4,
  3. A Bardier5,
  4. F Charlotte5,
  5. J-C Vaillant6,
  6. F Ménégaux7,
  7. M Rosenzwajg1,2,
  8. F Lemoine1,2,
  9. D Klatzmann1,2,
  10. J Taieb1,2,4
  1. 1
    Département de Biothérapie, Groupe Hospitalier Pitié Salpêtrière, Paris, France
  2. 2
    Laboratoire de Biologie et Thérapeutique des Pathologies Immunitaires, Centre National de la Recherche Scientifique-Unité Mixte de Recherche 7087, Université Pierre et Marie Curie-Paris 6, Hôpital Pitié-Salpêtrière, Paris, France
  3. 3
    Centre d’investigation clinique Biothérapie, CICBT507, Institut Gustave Roussy, Villejuif, France
  4. 4
    Service d’hépatogastro-entérologie, Hôpital Pitié-Salpêtrière, Paris, France
  5. 5
    Service d’anatomopathologie, Hôpital Pitié-Salpêtrière, Paris, France
  6. 6
    Service de chirurgie digestive et hépato-biliaire, Hôpital Pitié-Salpêtrière, Paris
  7. 7
    Service de chirurgie viscérale et digestive, Hôpital Pitié-Salpêtrière, Paris, France
  1. Professor J Taieb, Service d’hépatogastro-entérologie, Hôpital Européen Georges Pompidou, 20 rue Leblanc, 75015 PARIS, France; julien.taieb{at} or jtaieb{at}


Background: The antitumoral immune response is one determinant of colorectal cancer (CRC) outcome. Recent work suggests that Foxp3+CD25+CD4+ regulatory T cells (T4reg) might hamper effective immunosurveillance of emerging cancer cells and impede effective immune responses to established tumours. In this descriptive study, we analysed blood and tissue regulatory T cell populations in patients with CRC.

Methods: Blood and tissue regulatory Foxp3+ T cells from 40 patients with CRC were compared to regulatory Foxp3+ T cells from normal colonic tissue and from blood of 26 healthy volunteers. Flow cytometry was used to quantify and phenotype all Foxp3+ T cell populations. Correlations were sought with the tumour stage and with micro-invasive status. The suppressive capacity of regulatory Foxp3+ T cells was assessed by their effect on CD4+CD25 T cell proliferation in vitro and by their capacity to inhibit cytokine production by conventional T cells.

Results: We found a significant increase of CD8+CD25+Foxp3+ cells (T8reg) in blood and CRC tissue; their phenotype was close to that of T4reg. T8reg cells infiltrating CRC were activated, as suggested by increased cytoxic T lymphocyte-associated antigen-4, glucocorticoid-induced tumour necrosis factor-related protein, and transforming growth factor (TGF)β1 expression compared to T8reg from normal autologous colonic tissue. Moreover, T8reg were able to suppress CD4+CD25 T cell proliferation and Th1 cytokine production ex vivo, demonstrating that tumour-infiltrating T8reg have strong suppressive capacities. T8reg numbers correlated with the tumour stage and with micro-invasive status. Finally, interleukin 6 and TGFβ1 synergistically induced the generation of CD8+CD25+Foxp3+ T cells ex vivo.

Conclusions: We have identified a new regulatory T cell population (CD8+Foxp3+) in colorectal tumours. After isolation from cancer tissue these CD8+Foxp3+ cells demonstrated strong immunosuppressive properties in vitro. These data suggest that these cells may contribute to tumoral immune escape and disease progression.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Competing interests: None.

  • Funding: This work was supported by Institut Fédératif de Recherche 113 (IFR 113), Université Pierre et Marie Curie-Paris 6. SL was supported by Fondation pour la Recherche Médicale.

  • Ethics approval: The study was approved by the Pitié Salpétrière Hospital Ethics Committee on 14 November 2005.

Linked Articles

  • Digest
    Robin Spiller Magnus Simren