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

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.

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