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

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 has been found to additionally possess the ability to control tissue homeostasis and repair. However, it is not known how these functions are molecularly controlled and if 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 towards 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 the potential for targeted modulation of Treg cell functions, offering new avenues for cancer therapy. 2x105 B16.F10 cells were inoculated in wild-type mice (WT; Csnk2bfl/fl) and Foxp3-Cre × CK2b-fl/fl (KO; Csnk2bTreg-/-) mice (8–16 weeks old). B16.F10 tumors of comparable size were isolated on day 15 after inoculation B16.F10 tumors of comparable size were isolated on day 15 after inoculation, fixed in formalin and embedded in paraffin. Tissue sections were analyzed using spatial transcriptomics.