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RESEARCH PRODUCT
Regulatory T Cells in an Endogenous Mouse Lymphoma Recognize Specific Antigen Peptides and Contribute to Immune Escape.
Vera BauerNadine HömbergFatima AhmetlićTim SparwasserTanja RiedelRalph MocikatStefan StevanovicNico TrautweinMartin RöckenAlbert Geishausersubject
0301 basic medicineGenetically modified mouseCancer ResearchLymphoma B-CellImmunologychemical and pharmacologic phenomenaMice TransgenicT-Lymphocytes RegulatoryEpitope03 medical and health sciences0302 clinical medicineAntigenCell Line TumorMHC class ImedicineAnimalsAntigensbiologyEffectorFOXP3hemic and immune systemsmedicine.diseaseLymphomaMice Inbred C57BL030104 developmental biologyTumor Escape030220 oncology & carcinogenesisCancer researchbiology.proteinTumor EscapePeptidesdescription
Abstract 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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2019-03-20 | Cancer immunology research |