Kv11.1-dependent senescence activates a lethal immune response via tumor necrosis factor alpha

Abstract

Understanding the complex relationship between cancer and immune surveillance is essential for leveraging the immune system to control tumor growth. In our study, we discovered that activating the Kv11.1 potassium channel in ER+ breast cancer cells induces a senescent phenotype, which in turn triggers a potent immune response against these senescent cells. Specifically, we found that the senescence-associated secretory phenotype (SASP) plays a crucial role in activating CD4+ T-helper 1 (Th1) cells and memory T cell phenotypes. This activation led to the release of tumor necrosis factor-alpha (TNFα), which induced the death of senescent breast cancer cells, independent of their resistance to endocrine therapy. Our findings suggest that Kv11.1 channel-induced cellular senescence in ER+ breast cancer cells is a key mechanism in immune surveillance, driving a lethal immune response through TNFα. These results highlight the potential immunomodulatory role of Kv11.1 activation in ER-positive breast cancer and provide a foundation for future therapeutic investigations.