Work from University of Cincinnati researchers has found that by targeting the KCa 3.1 potassium channel, CD8+ T cells may have a better shot at infiltrating tumors. Their work was published in Science Signaling yesterday.
"Reduced potassium channel activity curbs T cell movement within the tumor," says Laura Conforti, corresponding author of the study. "T cell infiltration in solid tumors is limited by multiple factors found within the tumor's microenvironment, including adenosine, an immunosuppressive substance accumulating in high amounts in solid tumors."
Study leader Ameet Chimote, Conforti, and the team looked at migration patterns of CD8+ T cells in a 3D model that allowed some reproduction of a tumor microenvironment. They found that when adenosine was present, the movement of T cells from cancer patients was inhibited more than T cells from healthy donors.
"The increased sensitivity of patient CD8+ T cells to adenosine correlated with reduced KCa3.1 channel activity, but not with adenosine receptor expression or signaling," Conforti says. "Treatment with a substance that restores the KCa3.1 channel activity corrects patient CD8+ T cell migration in the presence of adenosine, suggesting that potassium channel activators may help enhance T cell infiltration of adenosine-rich solid tumors, providing another therapy option. This finding could lead to the development of new therapeutic agents to use in combination with approved immunomodulators for the treatment of solid tumors, as they may improve their efficacy."