Antigen-specific Tregs control T cell responses against a limited repertoire of tumor antigens in patients with colorectal carcinoma

Andreas Bonertz, Jürgen Weitz, Dong Ho Kim Pietsch, Nuh N. Rahbari, Christoph Schlude, Yingzi Ge, Simone Juenger, Israel Vlodavsky, Khashayarsha Khazaie, Dirk Jaeger, Christoph Reissfelder, Dalibor Antolovic, Maximilian Aigner, Moritz Koch, Philipp Beckhove

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)3311-3321
Number of pages11
JournalJournal of Clinical Investigation
Volume119
Issue number11
DOIs
StatePublished - Nov 2 2009
Externally publishedYes

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Neoplasm Antigens
Colorectal Neoplasms
T-Lymphocytes
Antigens
Neoplasms
Immunotherapy
Autoimmune Diseases
Healthy Volunteers
Peptides
Survival

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Antigen-specific Tregs control T cell responses against a limited repertoire of tumor antigens in patients with colorectal carcinoma. / Bonertz, Andreas; Weitz, Jürgen; Pietsch, Dong Ho Kim; Rahbari, Nuh N.; Schlude, Christoph; Ge, Yingzi; Juenger, Simone; Vlodavsky, Israel; Khazaie, Khashayarsha; Jaeger, Dirk; Reissfelder, Christoph; Antolovic, Dalibor; Aigner, Maximilian; Koch, Moritz; Beckhove, Philipp.

In: Journal of Clinical Investigation, Vol. 119, No. 11, 02.11.2009, p. 3311-3321.

Research output: Contribution to journalArticle

Bonertz, A, Weitz, J, Pietsch, DHK, Rahbari, NN, Schlude, C, Ge, Y, Juenger, S, Vlodavsky, I, Khazaie, K, Jaeger, D, Reissfelder, C, Antolovic, D, Aigner, M, Koch, M & Beckhove, P 2009, 'Antigen-specific Tregs control T cell responses against a limited repertoire of tumor antigens in patients with colorectal carcinoma', Journal of Clinical Investigation, vol. 119, no. 11, pp. 3311-3321. https://doi.org/10.1172/JCI39608
Bonertz, Andreas ; Weitz, Jürgen ; Pietsch, Dong Ho Kim ; Rahbari, Nuh N. ; Schlude, Christoph ; Ge, Yingzi ; Juenger, Simone ; Vlodavsky, Israel ; Khazaie, Khashayarsha ; Jaeger, Dirk ; Reissfelder, Christoph ; Antolovic, Dalibor ; Aigner, Maximilian ; Koch, Moritz ; Beckhove, Philipp. / Antigen-specific Tregs control T cell responses against a limited repertoire of tumor antigens in patients with colorectal carcinoma. In: Journal of Clinical Investigation. 2009 ; Vol. 119, No. 11. pp. 3311-3321.
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