IMPLICATION OF HIGHLY CYTOTOXIC NATURAL KILLER CELLS FOR ESOPHAGEAL CANCER TREATMENT

Abstract

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive solid tumors with limited therapeutic options. Here, we studied the potential of ex-vivo expanded NK cell (NKAES NK)-based immunotherapy for ESCC treatment. We first analyzed both genetic and surface expression of NKG2D ligands in ESCC. We also compared cytotoxicity between NKAES NK cells, IL-2-activated NK cells and resting NK cells against ESCC cell lines. We then investigated the effect of EMT inducers, GSK3β inhibitor and EGF, on NKG2DLs expressions in ESCC cell lines. Lastly, we determined the importance of IL-2 augmentation for boosting NK cell function in the presence of TGFβ1. As a result, MICA and MICB were significantly overexpressed in ESCC compared with adjacent normal tissues and NKG2DLs were expressed in ESCC cell lines. NKAES NK cells were the most potent NK cell against ESCC cell lines compared with IL-2-activated NK cells and resting NK cells. Furthermore, EMT inducers concurrently induced EMT conversion and NKG2DLs expression in ESCC cell lines rendering transitioned cells more sensitive to NKAES NK cells. IL-2 augmentation significantly enhanced NK cell cytotoxicity, particularly NKAES NK cells, against ESCC cell lines in the presence of TGFβ1. In summary, these results provide a strong rationale for clinical use of NKAES NK cells in ESCC patients.