Kv1.3 channels mark functionally competent CD8+ tumor infiltrating lymphocytes in head and neck cancer.

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Kv1.3 channels mark functionally competent CD8+ tumor infiltrating lymphocytes in head and neck cancer.

Cancer Res. 2016 Nov 4;:

Authors: Chimote AA, Hajdu P, Sfyris AM, Gleich BN, Wise-Draper T, Casper KA, Conforti L

Abstract
Tumor infiltrating lymphocytes (TIL) are potent mediators of an anti-tumor response. However, their function is attenuated in solid tumors. CD8(+) T cell effector functions such as cytokine and granzyme production depend on cytoplasmic Ca(2+), which is controlled by ion channels. In particular, Kv1.3 channels regulate the membrane potential and Ca(2+) influx in human effector memory T (TEM) cells. In this study, we assessed the contribution of reduced Kv1.3 and Ca(2+) flux on TIL effector function in head and neck cancer (HNC). We obtained tumor samples and matched peripheral blood from 14 patients with HNC. CD3(+) TIL were comprised of 57% CD4(+) (82% TEM and 20% Treg) and 36% CD8(+) cells. Electrophysiology revealed a 70% reduction in functional Kv1.3 channels in TIL as compared to peripheral blood T cells from paired patients, which was accompanied by a decrease in Ca(2+) influx. Immunofluorescence analysis showed that CD8(+) TIL expressing high Kv1.3 preferentially localized in the stroma. Importantly, high expression of Kv1.3 correlate with high Ki-67 and granzyme B expression. Overall, these data indicate that defective Kv1.3 channels and Ca(2+) fluxes in TIL may contribute to reduced immune surveillance in HNC.

PMID: 27815390 [PubMed - as supplied by publisher]

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