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Regulatory T cells in an endogenous mouse lymphoma recognize specific antigen peptides and contribute to immune escape.
Cancer Immunol. Res. 7, 600-608 (2019)
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Foxp3+ regulatory T cells (Tregs) sustain immune homeostasis and may contribute to immune escape in malignant disease. As a prerequisite for developing immunologic approaches in cancer therapy, it is necessary to understand the ontogeny and the antigenic specificities of tumor-infiltrating Tregs. We addressed this question by using a λ-MYC transgenic mouse model of endogenously arising B-cell lymphoma, which mirrors key features of human Burkitt lymphoma. We show that Foxp3+ Tregs suppress antitumor responses in endogenous lymphoma. Ablation of Foxp3+ Tregs significantly delayed tumor development. The ratio of Treg to effector T cells was elevated in growing tumors, which could be ascribed to differential proliferation. The Tregs detected were mainly natural Tregs that apparently recognized self-antigens. We identified MHC class II-restricted nonmutated self-epitopes, which were more prevalent in lymphoma than in normal B cells and could be recognized by Tregs. These epitopes were derived from proteins that are associated with cellular processes related to malignancy and may be overexpressed in the tumor.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Selective Depletion; Ifn-gamma; Tolerance; Receptor; Self; Reg; Activation; Mechanisms; Expression; Survival
Language
english
Publication Year
2019
HGF-reported in Year
2019
ISSN (print) / ISBN
2326-6066
e-ISSN
2326-6074
Journal
Cancer Immunology Research
Quellenangaben
Volume: 7,
Issue: 4,
Pages: 600-608
Publisher
American Association for Cancer Research (AACR)
Publishing Place
Philadelphia, Pa.
Reviewing status
Peer reviewed
POF-Topic(s)
30203 - Molecular Targets and Therapies
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s)
Immune Response and Infection
PSP Element(s)
G-501711-001
G-501700-001
G-501700-001
WOS ID
WOS:000462983600008
Scopus ID
85064143075
PubMed ID
30894379
Erfassungsdatum
2019-03-23