Role of Hv1 channel in cancer immunoprotection and malignancy.

Hv1 is linked to immunosuppression mediated by MDSC through the modulation of function of NOX2. The carcinogenesis process includes several changes to local temperature, pain and, especially important, pH. We studied the relation of Hv1 activity within melanoma in murine model by using, flow-cytometry, biochemistry and patch-clamp in whole cell configuration. In this work, we demonstrated that the inhibition of the Hv1 by its canonical blockers (Zn+2 and Cl-GBI) reduces the ROS production on MDSC which in turn decreases immunosuppression around the tumor mass. By inducing the growth of melanoma B16F0 in mice by inoculation and then treating the animals with the Hv1 inhibitors we found a dramatic reduction on tumor mass volume (∼35%). These results suggest that the inhibition of Hv1 activity promotes the immune response within the model, in turn, reducing the growth rate of the tumoral mass. On the other hand, MDSC present an increment on Hv1 expression through their differentiation process maximizing when reaching its final stages as dendritic cells or neutrophiles. By using non-stationary noise analysis of Hv1 channel we calculated the number of channels present in the cells when reaching their MDSC stage to 9 channel/µm. However, when comparing samples of cancer with different malignancy (HeLa vs B16F0), the levels of expression of Hv1 shows a stark difference. Our result suggest that the degrees of malignancy seem to be directly proportional to the expression of Hv1. Setting Hv1 as both a prognosis marker for cancer and a potential therapeutic target