Dissecting the role of Kv1.3 in the cross-talk between melanoma cells and macrophages

Voltage-gated potassium channels (Kv) are a class of ion channels that play pivotal roles in both physiological and pathological processes, including carcer. Among them, Kv1.3, is highly expressed in immune cells, neurons, as well as tumor cells. In these contexts, it regulates key cellular processes, as cell cycle progression, mitochondrial homeostasis, and cell volume. Indeed, Kv1.3 ablation in B16F10 melanoma cells led to a marked reduction in tumor growth in vivo. Additionally, Kv1.3 has been shown to modulate macrophages activation and function. Our preliminary experiments suggest a cross-talk between macrophages in the tumor microenvironment and melanoma cells. However, whether the expression of Kv1.3 in tumor cells influences the behaviour of macrophages remains unclear. Therefore, the aim of this project is to investigate if and how melanoma tumor cells reshape and reprogram macrophage phenotypes, through their Kv1.3 expression, and to dissect the cross-talk between tumor cells and macrophages. For this purpose, we generated tumor-conditioned media from wildtype and Kv1.3 knock-down B16F10 cells and assessed whether it differentially affected macrophage polarization and migration. Our results show that the Kv1.3 expression in melanoma cells does not alter the secretion of factors capable of influencing macrophages polarization or migration. However, we cannot exclude the possibility that the presence of Kv1.3 in tumor cells could modulate macrophages activation through cell-to-cell interactions, rather than through the secretions of soluble factors. This possibility will be tested in the future using co-culture experiments.