Antigen-specific Tregs control T cell responses against a limited repertoire of tumor antigens in patients with colorectal carcinoma.
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.
Bonertz
Andreas
A
Translational Immunology Unit, The German Cancer Research Center, Heidelberg, Germany.
Weitz
Jürgen
J
Pietsch
Dong-Ho Kim
DH
Rahbari
Nuh N
NN
Schlude
Christoph
C
Ge
Yingzi
Y
Juenger
Simone
S
Vlodavsky
Israel
I
Khazaie
Khashayarsha
K
Jaeger
Dirk
D
Reissfelder
Christoph
C
Antolovic
Dalibor
D
Aigner
Maximilian
M
Koch
Moritz
M
Beckhove
Philipp
P
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*
D000951:Antigens, Neoplasm; D010455:Peptides