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- Title
Antigen-specific Tregs control T cell responses against a limited repertoire of tumor antigens in patients with colorectal carcinoma.
- Authors
Bonertz, Andreas; Weitz, Jürgen; Pietsch, Dong-Ho Kim; Rahbari, Nuh N.; Schlude, Christoph; Yingzi Ge; Juenger, Simone; Vlodavsky, Israel; Khazaie, Khashayarsha; Jaeger, Dirk; Reissfelder, Christoph; Antolovic, Dalibor; Aigner, Maximilian; Koch, Moritz; Beckhove, Philipp; Weitz, Jürgen; Ge, Yingzi
- Abstract
Spontaneous antitumor T cell responses in cancer patients are strongly controlled by Tregs, and increased numbers of tumor-infiltrating Tregs correlate with reduced survival. However, the tumor antigens recognized by Tregs in cancer patients and the impact of these cells on tumor-specific T cell responses have not been systematically characterized. Here we used a broad panel of long synthetic peptides of defined tumor antigens and normal tissue antigens to exploit a newly developed method to identify and compare ex vivo the antigen specificities of Tregs with those of effector/memory T cells in peripheral blood of colorectal cancer patients and healthy subjects. Tregs in tumor patients were highly specific for a distinct set of only a few tumor antigens, suggesting that Tregs exert T cell suppression in an antigen-selective manner. Tumor-specific effector T cells were detectable in the majority of colorectal cancer patients but not in healthy individuals. We detected differences in the repertoires of antigens recognized by Tregs and effector/memory T cells in the majority of colorectal cancer patients. In addition, only effector/memory T cell responses against antigens recognized by Tregs strongly increased after Treg depletion. The selection of antigens according to preexisting T cell responses may improve the efficacy of future immunotherapies for cancer and autoimmune disease.
- Subjects
ANTIGENS; T cells; TUMOR antigens; COLON cancer; CANCER patients; AUTOIMMUNE diseases
- Publication
Journal of Clinical Investigation, 2009, Vol 119, Issue 11, p3311
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI39608