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

• Published in: The Journal of clinical investigation Vol. 119; no. 11; pp. 3311 - 3321
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 01.11.2009
• Subjects: Amino Acid Sequence; Antigens; Antigens, Neoplasm - chemistry; Antigens, Neoplasm - immunology; Biomedical research; Care and treatment; Colorectal cancer; Colorectal Neoplasms - immunology; Development and progression; Genetic aspects; Health aspects; Histocompatibility Testing; Humans; Immunotherapy; Lymphocyte Depletion; Lymphocytes; Medical prognosis; Molecular Sequence Data; Peptides - metabolism; Polypeptides; T cells; T-Lymphocytes - immunology; T-Lymphocytes, Regulatory - immunology; United States; Germany
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI39608

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.