Kv1.3 Channels Mark Functionally Competent CD8+ Tumor-Infiltrating Lymphocytes in Head and Neck Cancer.
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% TEMand 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. ©2016 AACR.
Department of Internal Medicine, Division of Nephrology, University of Cincinnati, Cincinnati, Ohio.
Ameet A
AA
Chimote
Department of Internal Medicine, Division of Nephrology, University of Cincinnati, Cincinnati, Ohio.
Peter
P
Hajdu
Department of Internal Medicine, Division of Nephrology, University of Cincinnati, Cincinnati, Ohio.
Alexandros M
AM
Sfyris
Department of Internal Medicine, Division of Nephrology, University of Cincinnati, Cincinnati, Ohio.
Brittany N
BN
Gleich
Department of Internal Medicine, Division of Hematology/Oncology, University of Cincinnati, Cincinnati, Ohio.
Trisha
T
Wise-Draper
Department of Otolaryngology, University of Michigan, Ann Arbor, Michigan.
Keith A
KA
Casper
Department of Internal Medicine, Division of Nephrology, University of Cincinnati, Cincinnati, Ohio. laura.conforti@uc.edu.
Laura
L
Conforti
D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D002469:Cell Separation; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006258:Head and Neck Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D051664:Kv1.3 Potassium Channel / Q000378:metabolism*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018408:Patch-Clamp Techniques; D000077195:Squamous Cell Carcinoma of Head and Neck
D051664:Kv1.3 Potassium Channel; D002118:Calcium