Abstract
Despite tremendous advances in oncology, metastatic triple-negative breast cancer remains difficult to treat and manage with established therapies. Here, we show in mice with orthotopic triple-negative breast tumors that alternating (100 kHz), and low intensity (<1 mV/cm) induced electric fields (iEFs) significantly reduced primary tumor growth and distant lung metastases. Non-contact iEF treatment can be delivered safely and non-invasively in vivo via a hollow, rectangular solenoid coil. We discovered that iEF treatment enhances anti-tumor immune responses at both the primary breast and secondary lung sites. In addition, iEF reduces immunosuppressive TME by reducing effector CD8+ T cell exhaustion and the infiltration of immunosuppressive immune cells. Furthermore, iEF treatment reduced lung metastasis by increasing CD8+ T cells and reducing immunosuppressive Gr1+ neutrophils in the lung microenvironment. We also observed that iEFs reduced the metastatic potential of cancer cells by inhibiting epithelial-to-mesenchymal transition. By introducing a non-invasive and non-toxic electrotherapeutic for inhibiting metastatic outgrowth and enhancing anti-tumor immune response in vivo, treatment with iEF technology could add to a paradigm-shifting strategy for cancer therapy.