American Association for Cancer Research
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Supplementary Figure Legends from Transient Ablation of Regulatory T cells Improves Antitumor Immunity in Colitis-Associated Colon Cancer

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posted on 2023-03-30, 22:34 authored by Eva Pastille, Katrin Bardini, Diana Fleissner, Alexandra Adamczyk, Annika Frede, Munisch Wadwa, Dorthe von Smolinski, Stefan Kasper, Tim Sparwasser, Achim D. Gruber, Martin Schuler, Shimon Sakaguchi, Axel Roers, Werner Müller, Wiebke Hansen, Jan Buer, Astrid M. Westendorf

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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. Cancer Res; 74(16); 4258–69. ©2014 AACR.

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