Regulatory T Cells in an Endogenous Mouse Lymphoma Recognize Specific Antigen Peptides and Contribute to Immune Escape

Abstract

Foxp3 þ 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 l-MYC transgenic mouse model of endogenously arising B-cell lymphoma, which mirrors key features of human Burkitt lymphoma. We show that Foxp3 þ Tregs suppress antitumor responses in endogenous lymphoma. Ablation of Foxp3 þ 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 selfantigens. 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.

Cancer immune control needs senescence induction by interferon-dependent cell cycle regulator pathways in tumours

“…We detected no CD8 + T cells and no CD49b + NK cells ( Supplementary Fig. 6d), what may be due to the fact that NK cells are primarily found in the spleen 40,41 . As ICB induced a similar immune infiltrate in RT2cancers and in Stat1-and Cdkn2a-deficient RT2-cancers ( Supplementary Fig.…”

“…Lymphoma-specific, regulatory T cells are also increased in the spleen. Yet, depletion of regulatory T cells delays lymphoma development and death only for a short time 40 .…”

Regulatory T cells in tumor microenvironment: new mechanisms, potential therapeutic strategies and future prospects

“…Ablation of Foxp3 + Tregs significantly delayed tumour development. The ratio of Tregs to effector T cells was elevated in growing tumours [ 136 ]. The infiltration of T cells into the TME represents a critical bottleneck for immune-mediated control of cancer.…”

<p>Major histocompatibility complex class II molecule in non-small cell lung cancer diagnosis, prognosis and treatment</p>

“…However, MHC class II-restricted antigen presentation may not always have positive effects on antitumor immunity. A study in mice found that nonmutated self-epitopes that might be overexpressed in tumor cells could be presented by MHC class II and be recognized by Tregs, which could suppress the antitumor response of the host 30. Another study showed that the antigen presented by tumor cells through MHC class II could alter tumor antigen specific T cells into Tregs and restrict the ability to eliminate tumor cells 31…”