Amphiregulin couples IL1RL1+ regulatory T cells and cancer-associated fibroblasts to inhibit antitumor immunity

We demonstrated that IL-33 induced strong CD8+ T cell antitumor immune responses characterized by robust clonal expansion and vigorous functional diversification. Nonetheless, IL-33 also produced intense regulatory T cell (Treg) accumulation in the TME, dominated by the IL1RL1+ Treg subset. We further showed that IL1RL1 signaling in Treg cells greatly dampened the antitumor activity of IL-33. Paired single cell RNA-seq and TCR-seq from FACS sorted T cells from mouse transplant melanoma B16 and IL-33 expressing B16-IL33 tumors.