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Cancer Res. 2017 Jan 1;77(1):53-61. doi: 10.1158/0008-5472.CAN-16-2372. Epub 2016 Nov 4.

Kv1.3 Channels Mark Functionally Competent CD8+ Tumor-Infiltrating Lymphocytes in Head and Neck Cancer.

Author information

1
Department of Internal Medicine, Division of Nephrology, University of Cincinnati, Cincinnati, Ohio.
2
Department of Internal Medicine, Division of Hematology/Oncology, University of Cincinnati, Cincinnati, Ohio.
3
Department of Otolaryngology, University of Michigan, Ann Arbor, Michigan.
4
Department of Internal Medicine, Division of Nephrology, University of Cincinnati, Cincinnati, Ohio. laura.conforti@uc.edu.

Abstract

Tumor-infiltrating lymphocytes (TIL) are potent mediators of an antitumor response. However, their function is attenuated in solid tumors. CD8+ T-cell effector functions, such as cytokine and granzyme production, depend on cytoplasmic Ca2+, which is controlled by ion channels. In particular, Kv1.3 channels regulate the membrane potential and Ca2+ influx in human effector memory T (TEM) cells. In this study, we assessed the contribution of reduced Kv1.3 and Ca2+ 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+ TILs were composed of 57% CD4+ (82% TEM and 20% Tregs) and 36% CD8+ cells. Electrophysiology revealed a 70% reduction in functional Kv1.3 channels in TILs as compared with peripheral blood T cells from paired patients, which was accompanied by a decrease in Ca2+ influx. Immunofluorescence analysis showed that CD8+ TILs expressing high Kv1.3 preferentially localized in the stroma. Importantly, high expression of Kv1.3 correlated with high Ki-67 and granzyme B expression. Overall, these data indicate that defective Kv1.3 channels and Ca2+ fluxes in TILs may contribute to reduced immune surveillance in HNC. Cancer Res; 77(1); 53-61.

PMID:
27815390
PMCID:
PMC5215046
DOI:
10.1158/0008-5472.CAN-16-2372
[Indexed for MEDLINE]
Free PMC Article

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