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    Transient ablation of regulatory T cells improves antitumor immunity in colitis-associated colon cancer (2014)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Pastille, Eva
    Bardini, Katrin
    Fleissner, Diana
    Adamczyk, Alexandra
    Frede, Annika
    Wadwa, Munisch
    von Smolinski, Dorthe (WE 12)
    Kasper, Stefan
    Sparwasser, Tim
    Gruber, Achim D (WE 12)
    Schuler, Martin
    Sakaguchi, Shimon
    Roers, Axel
    Müller, Werner
    Hansen, Wiebke
    Buer, Jan
    Westendorf, Astrid M
    Quelle
    Cancer research; 74(16) — S. 4258–4269
    ISSN: 0008-5472
    Sprache
    Englisch
    Verweise
    DOI: 10.1158/0008-5472.CAN-13-3065
    Pubmed: 24906621
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    Abstract / Zusammenfassung

    Regulatory T cells (Treg) are supportive to cancer development in most tissues, but their role in colitis-associated colon cancer (CAC) remains unclear. In this study, we investigated the role of CD4(+)Foxp3(+) Treg in a mouse model of CAC and in patients with colon cancer. These Treg were increased strongly in number in a mouse model of CAC and in the peripheral blood of patients with colon cancer, exhibiting an activated phenotype as defined by elevated expression of GARP, CD103, CTLA-4, and IL10, along with an increased suppressive effect on the proliferation and Th1 cytokine expression of CD4(+)CD25(-) responder T cells ex vivo. Transient ablation of CD4(+)Foxp3(+) Treg during tumor development in the CAC model suppressed tumor outgrowth and distribution, accompanied by an increased number of CD8(+)IFNγ/granzyme B-producing effector T cells. Conversely, inactivation of IL10 in Treg did not elevate the antitumor response but instead further boosted tumor development. Our results establish a tumor-promoting function for Treg during CAC formation, but they also suggest that a selective, transient ablation of Treg can evoke antitumor responses, with implications for immunotherapeutic interventions in patients with CAC.