Identification of CD8+CD25+Foxp3+ suppressive T cells in colorectal cancer tissue. - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Gut Année : 2009

Identification of CD8+CD25+Foxp3+ suppressive T cells in colorectal cancer tissue.

Résumé

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)beta1 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 TGF beta 1 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.

Domaines

Immunothérapie

Dates et versions

hal-00420200 , version 1 (28-09-2009)

Identifiants

Citer

N. Chaput, S. Louafi, A. Bardier, F. Charlotte, J.-C. Vaillant, et al.. Identification of CD8+CD25+Foxp3+ suppressive T cells in colorectal cancer tissue.. Gut, 2009, 58 (4), pp.520-9. ⟨10.1136/gut.2008.158824⟩. ⟨hal-00420200⟩
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