High-Intensity Focused Ultrasound Elevates Il-2rb on CD8+ T Cells: Enhancing JAK-STAT and IL‑2 Efficacy in Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) is characterized by a lack of effective targeted therapies and a challenging immunosuppressive microenvironment that limits the efficacy of immunotherapy. This study explores the potential of high-intensity focused ultrasound (HIFU) in modulating the immune response. Using the 4T1 mouse tumor model, we assessed the effects of thermal (T-HIFU) and mechanical (M-HIFU) HIFU on CD8+ T cells. Proteomic analysis revealed that T-HIFU and M-HIFU increased Il-2rb expression on CD8+ T cells, activating the JAK-STAT pathway and enhancing the efficacy of IL-2, leading to improved tumor growth inhibition and survival rates. The combination of HIFU and IL-2 demonstrated synergistic antitumor effects, indicating a new strategy for enhancing immunotherapy in TNBC. This approach uniquely boosts antitumor immunity by upregulating Il-2rb on CD8+ T cells, offering a promising avenue for overcoming the immunosuppression in TNBC.