are employees of Bean Stalk Snow Co Ltd. The rest of the authors declare that they have no relevant conflicts of interest.

No abstract

Hypoxia (H) in solid tumors contributes to decreased immunosurveillance via Kv1.3 channel downregulation and inhibition of T cell function. However, the mechanisms responsible for Kv1.3 downregulation are not understood. We tested the hypothesis that chronic H (CH) reduces Kv1.3 surface expression via alterations in membrane trafficking. Jurkat T cells were maintained either in normoxia (21% O2) or H (1% O2) for 24h and Kv1.3 surface expression was quantified by in‐cell western blot analysis and flow cytometry using a specific Kv1.3 antibody against an extracellular epitope. CH decreased Kv1.3 surface expression in T cells by 25%. To study the involvement of endocytosis, endosome formation was blocked with Bafilomycin A1 (BAF). Comparable inhibition of Kv1.3 surface expression in CH was observed in BAF (27±4%) and control (ctr) (25±3%) cells. On the contrary, inhibition of the Golgi apparatus by Brefeldin A (BFE) prevented Kv1.3 surface expression reduction in CH (ctr 25±2% and BFE −4±3%). Furthermore, blockade of clathrin‐coated vesicle formation in the Golgi by dynasore (DYN), a selective dynamin inhibitor, prevented Kv1.3 surface expression decrease in CH (ctr 23±0.5% and DYN 0.93±1%). Our data suggest that CH disrupts forward trafficking of Kv1.3 protein from the Golgi to the plasma membrane thus contributing to the decrease in Kv1.3 surface expression in T lymphocytes. (NIH 2R01CA095286)