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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}egp.aphp.fr or jtaieb{at}club-internet.fr

Abstract

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.

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Footnotes

  • 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.

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