Exogenous IL-33 promotes tumor immunity via macroscopic regulation of ILC2s

Interleukin-33 (IL-33) is a pleiotropic molecule that plays various roles in the body. However, how exogenous IL-33 changes the tumor immune microenvironment remains unclear. Our study revealed that exogenous IL-33 exerts anti-tumor effects and effectively suppresses the progression of subcutaneous melanoma. scRNA-seq analysis revealed that exogenous IL-33 reduced neutrophils accumulation, thereby improving the inhibitory immune environment. Flow cytometry analysis revealed that exogenous IL-33 significantly increased the proportion of eosinophils and group 2 innate lymphoid cells (ILC2s). In addition, we identified genes encoding major histocompatibility complex (MHC) class II molecules in this group of ILC2s, suggesting that ILC2s may play a role in antigen presentation. In Il7r^CreArg1^flox/flox mice, the decrease of ILC2s led to a reduction in the proportion of eosinophils. Furthermore, we found that exogenous IL-33 effectively promoted the differentiation of ILC2s and their accumulation in tumors, thereby enhancing the anti-tumor immune response. These findings may pave the way for developing new cancer immunotherapies that use IL-33 as an activator to enhance anti-tumor immune responses.