2. Academic Validation
  3. Polyamines regulate adaptive antitumor immunity by functional specialization of regulatory T cells

Polyamines regulate adaptive antitumor immunity by functional specialization of regulatory T cells

  • Immunity. 2025 Aug 12;58(8):2019-2034.e11. doi: 10.1016/j.immuni.2025.07.007.
Georg Bündgen 1,  Alexander Ulges 1,  Jan Pietruschka 1,  Natalia Truong-Andrievici 1,  Matthias Klein 2,  Karolina Romaniuk 1,  Fabian Schmitt 1,  Mathias Hagen 1,  Joachim G Seebass 1,  Lenart Zezlina 1,  Lara Stein 1,  Hans Christian Probst 2,  Ute Distler 2,  Stefan Tenzer 3,  Michael Lohoff 4,  Addi J Romero-Olmedo 4,  Henrik Mei 5,  Toszka Bohn 2,  Michael Delacher 2,  Thierry Schmidlin 2,  Matthias M Gaida 6,  Ivan Dikic 7,  Charles Imbusch 8,  Hansjörg Schild 9,  Tobias Bopp 10
Affiliations

Affiliations

  • 1 University Medical Center Mainz, Institute of Immunology, 55131 Mainz, Germany.
  • 2 University Medical Center Mainz, Institute of Immunology, 55131 Mainz, Germany; Research Center for Immunotherapy (FZI), University Medical Center Mainz, 55131 Mainz, Germany.
  • 3 University Medical Center Mainz, Institute of Immunology, 55131 Mainz, Germany; Research Center for Immunotherapy (FZI), University Medical Center Mainz, 55131 Mainz, Germany; HI-Tron, DKFZ, 69120 Heidelberg, Germany.
  • 4 Philipps University Marburg, Institute for Medical Microbiology and Hospital Hygiene, 35043 Marburg, Germany.
  • 5 Deutsches Rheumaforschungszentrum Berlin, a Leibniz Institute, 10117 Berlin, Germany.
  • 6 Research Center for Immunotherapy (FZI), University Medical Center Mainz, 55131 Mainz, Germany; University Medical Center Mainz-Institute of Pathology, 55131 Mainz, Germany; University Cancer Center (UCT) Mainz, University Medical Center Mainz, 55131 Mainz, Germany; TRON, 55131 Mainz, Germany.
  • 7 Institute of Biochemistry II, Medical Faculty, Goethe University, 60590 Frankfurt am Main, Germany.
  • 8 University Medical Center Mainz, Institute of Immunology, 55131 Mainz, Germany; Research Center for Immunotherapy (FZI), University Medical Center Mainz, 55131 Mainz, Germany; Division of Applied Bioinformatics, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; Institute for Quantitative and Computational Biosciences (IQCB), 55128 Mainz, Germany; German Cancer Consortium (DKTK), 69120 Heidelberg, Germany.
  • 9 University Medical Center Mainz, Institute of Immunology, 55131 Mainz, Germany; Research Center for Immunotherapy (FZI), University Medical Center Mainz, 55131 Mainz, Germany; Centre for Healthy Ageing, Johannes Gutenberg University Mainz, 55128 Mainz, Germany.
  • 10 University Medical Center Mainz, Institute of Immunology, 55131 Mainz, Germany; Research Center for Immunotherapy (FZI), University Medical Center Mainz, 55131 Mainz, Germany; University Cancer Center (UCT) Mainz, University Medical Center Mainz, 55131 Mainz, Germany; Institute for Quantitative and Computational Biosciences (IQCB), 55128 Mainz, Germany; German Cancer Consortium (DKTK), 69120 Heidelberg, Germany; Centre for Healthy Ageing, Johannes Gutenberg University Mainz, 55128 Mainz, Germany. Electronic address: boppt@uni-mainz.de.
PMID: 40749666 DOI: 10.1016/j.immuni.2025.07.007
Abstract

In Cancer, metabolic changes and uncontrolled tumor growth alter nutrient availability, impacting antitumor immune responses. Regulatory T (Treg) cells are a subset of T cells with immunosuppressive properties that can also influence tissue homeostasis and repair. However, it is not known how these functions are molecularly controlled and whether they are influenced by tumor metabolism. Here, we report that excessive release of polyamines in the tumor microenvironment directs the functional polarization of Treg cells toward immunosuppression in a protein kinase CK2 (CK2)-dependent manner. Polyamine deprivation as well as genetic or pharmacological inhibition of CK2 activity in Treg cells induced tissue reparative properties in Treg cells that orchestrated efficient antitumor type 2 immune responses and coordinated tissue repair mechanisms to support tumor eradication. These findings suggest that targeted modulation of Treg cell functions could be leveraged as a potential avenue for Cancer therapy.

Keywords

FOXP3; cancer; immune evasion; immunometabolism; kinase; metabolism; polyamines; regulatory T cells; tissue repair; tumor immunology.

Figures
Products