Publikationsdatenbank

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

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
Gebäude 12
14163 Berlin
+49 30 838 62450

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.