Characterization of the role of Kv1.3 Potassium channel in Macrophages and regulatory T lymphocytes

Several evidences have documented a close relationship between ion channels and cancer, supporting a pivotal role for Potassium channels in cancer therapy. The voltage-gated potassium channel Kv1.3 is highly expressed in both nervous and immune system, and alterations in its expression or function were shown to be implicated in several diseases, including cancer. Therefore, we wanted to explore the role of Kv1.3 channel in two immune cells types that play a pivotal role in regulating the anti-tumor immune response: macrophages and regulatory T cells. To do that, the laboratory of prof. Szabó generated two tissue-specific conditional knock-out mouse models in which Kv1.3 was deleted in regulatory T cells and in the myeloid compartment respectively. Previous data in our lab indicated that deletion of Kv1.3 in myeloid cells increases the neutrophil to lymphocytes ratio, a prognostic marker frequently used in the clinic. Indeed, myeloid Kv1.3 knockout mice show boosted melanoma and breast tumor growth and higher M2 pro-tumoral macrophages infiltration. Furthermore Kv1.3 ablation modulates macrophages activation state, promoting their polarization towards the M2 phenotype. Regulatory T cells knock-out mice also show increased tumor burden and altered lymphocytes infiltration in the tumor microenvironment, suggesting a key role for Kv1.3 in regulating immune function.