1. Cytotoxicity of Human Hepatic Intrasinusoidal Gamma/Delta T Cells Depends on Phospho-antigen and NK Receptor Signaling
- Author
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Yoorha, Kang, Mina, Han, Minsong, Kim, Hyun Ju, Hwang, Byung Chan, Ahn, Eunyoung, Tak, Gi-Won, Song, Shin, Hwang, Kyung-Nam, Koh, Dong-Hwan, Jung, and Nayoung, Kim
- Subjects
Male ,Cytotoxicity, Immunologic ,Cancer Research ,Carcinoma, Hepatocellular ,Liver Neoplasms ,Receptors, Antigen, T-Cell, gamma-delta ,General Medicine ,Zoledronic Acid ,Diphosphates ,Oncology ,NK Cell Lectin-Like Receptor Subfamily K ,Cell Line, Tumor ,Leukocytes, Mononuclear ,Humans - Abstract
We previously showed that human hepatic intrasinusoidal (HI) natural killer (NK) T cells selectively eliminate hepatocellular carcinoma (HCC) cell lines. In this study, we investigated the underlying mechanisms on how HI γδ T cells, expanded with zoledronate, exhibit a superior cytotoxic effect on HI NK-resistant Huh7 HCC cells.γδ T cells were obtained from living liver transplant donors or from peripheral blood mononuclear cells (PBMC) of healthy volunteers and were expanded in the presence of IL-2, IL-15, and zoledronate for 2 weeks. Cytotoxicity was measured using the lactate dehydrogenase (LDH) assay in vitro and by flow cytometry using carboxyfluorescein succinimidyl ester (CFSE) in vivo.The cytotoxicity of expanded HI γδ T cells against Huh7 cells was associated with a higher pyrophosphate expression in Huh7 cells compared to SNU398 cells. In contrast, the cytotoxicity of HI γδ T cells against SNU398 cells depended on NKG2D. HI γδ T cells expressed less PD-1 than PB γδ T cells. The cytotoxicity of HI γδ T cells against Du145 and PC3 prostate cancer cells was also associated with pyrophosphate expression in these cells, as well as NKG2D and DNAM-1.The expression levels of phospho-antigen in tumor cells determined the cytotoxicity of HI γδ T cells, although the NK activating receptors, death ligands, and immune checkpoint molecules also contribute to their cytotoxicity. γδ T cells are attractive candidates for cancer immune cell therapy.
- Published
- 2022