title: Antigen-specific Tregs control T cell responses against a limited repertoire of tumor antigens in patients with colorectal carcinoma.
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.
authors.affiliation: Translational Immunology Unit, The German Cancer Research Center, Heidelberg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bonertz
authors.forename: Jürgen
authors.initials: J
authors.lastname: Weitz
authors.forename: Dong-Ho Kim
authors.initials: DH
authors.lastname: Pietsch
authors.forename: Nuh N
authors.initials: NN
authors.lastname: Rahbari
authors.forename: Christoph
authors.initials: C
authors.lastname: Schlude
authors.forename: Yingzi
authors.initials: Y
authors.lastname: Ge
authors.forename: Simone
authors.initials: S
authors.lastname: Juenger
authors.forename: Israel
authors.initials: I
authors.lastname: Vlodavsky
authors.forename: Khashayarsha
authors.initials: K
authors.lastname: Khazaie
authors.forename: Dirk
authors.initials: D
authors.lastname: Jaeger
authors.forename: Christoph
authors.initials: C
authors.lastname: Reissfelder
authors.forename: Dalibor
authors.initials: D
authors.lastname: Antolovic
authors.forename: Maximilian
authors.initials: M
authors.lastname: Aigner
authors.forename: Moritz
authors.initials: M
authors.lastname: Koch
authors.forename: Philipp
authors.initials: P
authors.lastname: Beckhove
mesh_terms: D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D008212:Lymphocyte Depletion; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D010455:Peptides