<p>Type II innate lymphoid cells (ILC2s) have been implicated in both tumor-promoting and tumor-suppressive functions, but the mechanism(s) underlying this functional heterogeneity is not clear. Here, we tested the hypothesis that signaling through β2-adrenergic receptor (β2-AR) drives the pro-tumor functions of ILC2s within the tumor microenvironment. Using global (β2AR⁻/⁻) and ILC2-specific conditional knockout (IL5^Creβ2AR^fl/fl) mouse models, we examined how β2-AR deficiency affects ILC2 function in breast cancer. We studied the impact of β2-AR function on ILC2 phenotype, gene profile, anti-tumor T cell response and breast tumor growth. β2AR inhibition resulted in an enrichment of KLRG1⁺ ILC2s with elevated GATA3 and ST2 expression in breast tumor. Loss of β2-AR signaling in ILC2s reduced their pro-tumorigenic activity and resulted in suppressed tumor growth. Additionally, β2-AR inhibition in ILC2s was associated with increased CD4⁺ T cell infiltration in breast tumors and a greater TNF-α⁺ CD8⁺ T cell response. β2-AR deficiency reprograms ILC2s toward a more immunostimulatory phenotype, promoting T cell-mediated anti-tumor immunity. These findings identify activity of the β2-AR as a key regulator of ILC2 plasticity and suggest β2-AR blockade as a promising strategy to enhance cancer immunotherapy.</p><p></p>