Polyamines regulate adaptive antitumor immunity by functional specialization of regulatory T cells
Georg Bündgen, Alexander Ulges, Jan Pietruschka, Natalia Truong-Andrievici, Matthias Klein, Karolina Romaniuk, Fabian Schmitt, Mathias Hagen, Joachim G Seebass, Lenart Zezlina, Lara Stein, Hans Christian Probst, Ute Distler, Stefan Tenzer, Michael Lohoff, Addi J. Romero‐Olmedo, Henrik E. Mei, Toszka Bohn, Michael Delacher, Thierry Schmidlin, Matthias M. Gaida, Ivan Đikić, Charles D. Imbusch, Hansjörg Schild, Tobias Bopp
Abstract
In cancer, metabolic changes and uncontrolled tumor growth alter nutrient availability, impacting antitumor immune responses. Regulatory T (T reg ) 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 T reg cells toward immunosuppression in a protein kinase CK2 (CK2)-dependent manner. Polyamine deprivation as well as genetic or pharmacological inhibition of CK2 activity in T reg cells induced tissue reparative properties in T reg 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 T reg cell functions could be leveraged as a potential avenue for cancer therapy.