Presentation description

Breast cancer is the most commonly diagnosed cancer in women, with metastasis being the leading cause of breast cancer-associated death. Immunotherapy has the potential to prevent and treat metastatic breast cancer, but strategies are urgently needed to enhance immune-mediated killing of metastatic tumors. Studies have identified a ligand-independent form of Ron kinase, short-form Ron (SF-Ron), as a key target for enhancing immune infiltration and treating metastatic breast cancer. Within a breast cancer bone metastasis model, wild-type and SF-Ron -/- mice have received an intratibial injection of PyMT tumor cells. By two weeks, both wild-type and SF-RON -/- mice had metastasis present; however, by four weeks, tumors persisted in wild-type mice but were eliminated in SF-Ron -/- mice. Deletion of SF-Ron (SF-Ron -/-) increases the accumulation of tumor-infiltrating immune cells, such as CD8+ cytotoxic T cells, and nearly eliminates breast cancer metastasis in mice. Immunohistochemical analysis confirmed a higher presence of CD8+ T cells in SF-Ron -/- mice at two weeks. When CD8+ T cells are removed from the SF-Ron -/- mice, a resurgence of tumors occurs, indicating the necessity of CD8+ T cells and their robust antitumor immune responses. These findings suggest that targeting SF-Ron could enhance CD8+ T cell-mediated immunity and offer a novel strategy for treating metastatic breast cancer.