RRC ID 56139
Author Lim KS, Mimura K, Kua LF, Shiraishi K, Kono K.
Title Implication of Highly Cytotoxic Natural Killer Cells for Esophageal Squamous Cell Carcinoma Treatment.
Journal J Immunother
Abstract Esophageal squamous cell carcinoma (ESCC) is an aggressive upper gastrointestinal cancer and effective treatments are limited. Previous studies reported that natural killer (NK) cells expanded by coculturing with K562-mb15-41BBL feeder cells, a genetically modified K562 leukemia cell line that expresses membrane-bound interleukin (IL)-15 and 41BBL ligand, were highly proliferative and highly cytotoxic. Here, we investigated the potential of expanded NK cells for ESCC treatment. We analyzed both genetic and surface expression levels of NKG2D ligands (NKG2DLs) in ESCC using publicly available microarray data sets and ESCC cell lines. The cytotoxicity of resting and of IL-2-activated NK cells against ESCC cell lines was compared with that of expanded NK cells. We then also investigated the effect of epithelial mesenchymal transition (EMT) inducers, GSK3β inhibitor and epidermal growth factor, on NKG2DLs expressions. As a result, MICA and MICB were significantly overexpressed in ESCC compared with adjacent normal tissues and surface NKG2DLs were expressed in ESCC cell lines. Expanded NK cells were much potent than IL-2-activated and resting NK cells against ESCC cell lines. Blocking of NKG2D with anti-NKG2D monoclonal antibody dampened expanded NK cell cytotoxicity, suggesting that the NKG2DLs-NKG2D interaction is crucial for NK cells to eliminate ESCC cells. EMT inducers concurrently induced EMT and NKG2DLs expression in ESCC cell lines rendering transitioned cells more sensitive to expanded NK cells. In conclusion, expanded NK cells were highly cytotoxic against NKG2DLs-expressing ESCC cells, particularly the EMT phenotype. These results provide a strong rationale for clinical use of these NK cells in ESCC patients.
Volume 41(6)
Pages 261-273
Published 2018-1-1
DOI 10.1097/CJI.0000000000000227
PMID 29683892
MeSH Antibodies, Monoclonal / metabolism Cancer Vaccines / immunology* Cell Proliferation Coculture Techniques Cytotoxicity, Immunologic Epithelial-Mesenchymal Transition Esophageal Neoplasms / immunology Esophageal Neoplasms / therapy* Esophageal Squamous Cell Carcinoma / immunology Esophageal Squamous Cell Carcinoma / therapy* Humans Immunotherapy, Adoptive / methods* Interleukin-1 / metabolism Interleukin-15 / metabolism K562 Cells Killer Cells, Natural / immunology* Killer Cells, Natural / transplantation Lymphocyte Activation NK Cell Lectin-Like Receptor Subfamily K / immunology NK Cell Lectin-Like Receptor Subfamily K / metabolism Signal Transduction
IF 3.455
Times Cited 3
Human and Animal Cells TE-14(RCB2101)