Research ArticleCell Biology

A defect in KCa3.1 channel activity limits the ability of CD8+ T cells from cancer patients to infiltrate an adenosine-rich microenvironment

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Science Signaling  24 Apr 2018:
Vol. 11, Issue 527, eaaq1616
DOI: 10.1126/scisignal.aaq1616

Reduced K+ channel activity curbs T cell migration

T cell accumulation in solid tumors is limited by multiple factors found within the tumor microenvironment, including the nucleoside adenosine. Chimote et al. analyzed the migration of CD8+ T cells in a 3D chemotaxis assay and found that adenosine inhibited the chemotaxis of T cells from cancer patients more than T cells from healthy donors. The increased sensitivity of patient CD8+ T cells to adenosine correlated with reduced KCa3.1 potassium (K+) channel activity, but not adenosine receptor expression or signaling. Treatment with a KCa3.1 channel agonist restored patient CD8+ T cell migration in the presence of adenosine, suggesting that K+ channel activators may help augment T cell infiltration of adenosine-rich solid tumors.