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Identification of CD8+CD25+Foxp3+ suppressive T cells in colorectal cancer tissue
  1. nathalie chaput
  1. Hopital de la Pitié Salpétrière, France
    1. Samy Louafi
    1. Hopital de la Pitié Salpétrière, France
      1. armelle Bardier
      1. Hopital de la Pitié Salpétrière, France
        1. frederic charlotte
        1. Hopital de la Pitié Salpétrière, France
          1. jean-christophe vaillant
          1. Hopital de la Pitié Salpétrière, France
            1. fabrice menegaux
            1. Hopital de la Pitié Salpétrière, France
              1. michelle rosenzwajg
              1. Hopital de la Pitié Salpétrière, France
                1. françois lemoine
                1. Hopital de la Pitié Salpétrière, France
                  1. david klatzmann
                  1. Hopital de la Pitié Salpétrière, France
                    1. julien taieb (jtaieb{at}club-internet.fr)
                    1. Georges Pompidou European Hospital, France

                      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 tumors. In this prospective study, we analyzed blood and tissue regulatory T cell populations in CRC patients.

                      Methods: Blood and tissue regulatory Foxp3+ T cells from 40 CRC patients were compared to regulatory Foxp3+ T cells from paired normal colonic tissue (NT) and from blood of healthy volunteers. Flow cytometry was used to quantify and phenotype all Foxp3+ T cell populations. Correlations were sought with the tumor 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 proliferation in vitro and by their capacity to inhibit cytokine production by conventional T cells.

                      Results: We found significant accumulation 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 CTLA-4, GITR and TGF-b1 expression compared to T8reg from paired normal tissue. Moreover, T8reg were able to suppress CD4+CD25- T cell proliferation and Th1 cytokine production ex vivo, demonstrating that tumor-infiltrating T8reg have strong suppressive capacities. T8reg numbers, but not T4reg numbers, correlated with the tumor stage and with micro-invasive status. Finally, IL-6 and TGF-b1 synergistically induced CD8+CD25+Foxp3+ T cell generation ex vivo.

                      Conclusions: We have identified a new regulatory T cell population (CD8+Foxp3+) with strong immunosuppressive properties in colorectal tumors. These cells may contribute to tumoral immune escape and disease progression.

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