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Ahmetlic, F. ; Riedel, T. ; Hömberg, N. ; Bauer, V. ; Trautwein, N.* ; Geishauser, A. ; Sparwasser, T.* ; Stevanović, S.* ; Röcken, M.* ; Mocikat, R.

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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