IL-23 stabilizes an effector Treg program in the tumor microenvironment

Regulatory T cells (Tregs) are crucial for the maintenance of immune tolerance and restrict immunopathology during inflammation, yet they limit efficient anti-tumor immunity in the tumor microenvironment (TME). Effector Tregs (eTregs) are thought to be the cellular subset equipped with the strongest immunosuppressive and cancer promoting properties. Here we found by in preclinical cancer models, that Treg specific deletion of IL23R reduces tumor growth. Using heterozygous conditional knock-out mice in which Il23r KO and Il23r WT Tregs coexist in the same tumor microenvironment, we found that IL-23 sensing represents a crucial signal driving the maintenance and stabilization of eTregs involving the transcription factor Foxp3. Overall design: single cell RNA sequencing of tumor infiltrating CD4+ T cells from female heterozygous Il23r conditional KO mice (Il23rfl/fl X Foxp3-Cre(+/-)) was performed on day 13 after tumor inoculation with B16F10 tumor cells.