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

被引:18
作者
Ahmetlic, Fatima [1 ,2 ]
Riedel, Tanja [2 ]
Hoemberg, Nadine [1 ,2 ]
Bauer, Vera [1 ]
Trautwein, Nico [3 ]
Geishauser, Albert [1 ,2 ]
Sparwasser, Tim [4 ,5 ]
Stevanovic, Stefan [3 ]
Roecken, Martin [6 ]
Mocikat, Ralph [1 ,2 ]
机构
[1] Helmholtz Zentrum Munchen, Eigenstandige Forsch Einheit Translat Mol Immunol, Munich, Germany
[2] Helmholtz Zentrum Munchen, Inst Mol Immunol, Munich, Germany
[3] Eberhard Karls Univ Tubingen, Interfak Inst Zellbiol, Tubingen, Germany
[4] Zentrum Expt & Klin Infekt Forsch, Institut Infekt Immunol, Twincore, Hannover, Germany
[5] Johannes Gutenberg Univ Mainz, Inst Med Mikrobiol & Hyg, Mainz, Germany
[6] Eberhard Karls Univ Tubingen, Univ Hautklin, Tubingen, Germany
关键词
SELECTIVE DEPLETION; IFN-GAMMA; TOLERANCE; RECEPTOR; SELF; REG; ACTIVATION; MECHANISMS; EXPRESSION; SURVIVAL;
D O I
10.1158/2326-6066.CIR-18-0419
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 lambda-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 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.
引用
收藏
页码:600 / 608
页数:9
相关论文
共 47 条
  • [1] Helios Expression Is a Marker of T Cell Activation and Proliferation
    Akimova, Tatiana
    Beier, Ulf H.
    Wang, Liqing
    Levine, Matthew H.
    Hancock, Wayne W.
    [J]. PLOS ONE, 2011, 6 (08):
  • [2] Critical role of the NKG2D receptor for NK cell-mediated control and immune escape of B-cell lymphoma
    Belting, Lena
    Hoemberg, Nadine
    Przewoznik, Margarethe
    Brenner, Christoph
    Riedel, Tanja
    Flatley, Andrew
    Polic, Bojan
    Busch, Dirk H.
    Roecken, Martin
    Mocikat, Ralph
    [J]. EUROPEAN JOURNAL OF IMMUNOLOGY, 2015, 45 (09) : 2593 - 2601
  • [3] Foxp3+ T Cells Induce Perforin-Dependent Dendritic Cell Death in Tumor-Draining Lymph Nodes
    Boissonnas, Alexandre
    Scholer-Dahirel, Alix
    Simon-Blancal, Virginie
    Pace, Luigia
    Valet, Fabien
    Kissenpfennig, Adrien
    Sparwasser, Tim
    Malissen, Bernard
    Fetler, Luc
    Amigorena, Sebastian
    [J]. IMMUNITY, 2010, 32 (02) : 266 - 278
  • [4] Transient regulatory T cell ablation deters oncogene-driven breast cancer and enhances radiotherapy
    Bos, Paula D.
    Plitas, George
    Rudra, Dipayan
    Lee, Sue Y.
    Rudensky, Alexander Y.
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2013, 210 (11) : 2435 - 2446
  • [5] Requirements for control of B-cell lymphoma by NK cells
    Brenner, Christoph D.
    King, Susan
    Przewoznik, Margarethe
    Wolters, Imke
    Adam, Christian
    Bornkamm, Georg W.
    Busch, Dirk H.
    Roecken, Martin
    Mocikat, Ralph
    [J]. EUROPEAN JOURNAL OF IMMUNOLOGY, 2010, 40 (02) : 494 - 504
  • [6] Regulatory T cells suppress tumor-specific CD8 T cell cytotoxicity through TGF-β signals in vivoi
    Chen, ML
    Pittet, MJ
    Gorelik, L
    Flavell, RA
    Weissleder, R
    von Boehmer, H
    Khazaie, K
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (02) : 419 - 424
  • [7] CD4+ CD25+ FOXP3+ Regulatory T Cells Suppress Anti-Tumor Immune Responses in Patients with Colorectal Cancer
    Clarke, Sarah L.
    Betts, Gareth J.
    Plant, Andrea
    Wright, Kate L.
    El-Shanawany, Tariq M.
    Harrop, Richard
    Torkington, Jared
    Rees, Brian I.
    Williams, Geraint T.
    Gallimore, Awen M.
    Godkin, Andrew J.
    [J]. PLOS ONE, 2006, 1 (02):
  • [8] Eliminating roles for T-bet and IL-2 but revealing superior activation and proliferation as mechanisms underpinning dominance of regulatory T cells in tumors
    Colbeck, Emily J.
    Hindley, James P.
    Smart, Kathryn
    Jones, Emma
    Bloom, Anja
    Bridgeman, Hayley
    McPherson, Rhoanne C.
    Turner, Darryl G.
    Ladell, Kristin
    Price, David A.
    O'Connor, Richard A.
    Anderton, Stephen M.
    Godkin, Andrew J.
    Gallimore, Awen M.
    [J]. ONCOTARGET, 2015, 6 (28) : 24649 - 24659
  • [9] Maintenance of immune tolerance by Foxp3+ regulatory T cells requires CD69 expression
    Cortes, Jose R.
    Sanchez-Diaz, Raquel
    Bovolenta, Elena R.
    Barreiro, Olga
    Lasarte, Sandra
    Matesanz-Marin, Adela
    Toribio, Maria L.
    Sanchez-Madrid, Francisco
    Martin, Filar
    [J]. JOURNAL OF AUTOIMMUNITY, 2014, 55 : 51 - 62
  • [10] Natural and Adaptive Foxp3+ Regulatory T Cells: More of the Same or a Division of Labor?
    de Lafaille, Maria A. Curotto
    Lafaille, Juan J.
    [J]. IMMUNITY, 2009, 30 (05) : 626 - 635