肿瘤细胞治疗研究
英文原题：Cytotoxicity of Human Hepatic Intrasinusoidal Gamma/Delta T Cells Depends on Phospho-antigen and NK Receptor Signaling.
Cytotoxicity of Human Hepatic Intrasinusoidal Gamma/Delta T Cells Depends on Phospho-antigen and NK Receptor Signaling.
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肿瘤细胞中磷酸抗原的表达水平决定了 HI γδ T 细胞的细胞毒性，尽管 NK 激活受体、死亡配体和免疫检查点分子也对其细胞毒性有所贡献。γδ T 细胞是癌症免疫细胞治疗的有吸引力的候选者。
我们之前的研究表明，人肝脏内窦状（HI）自然杀伤（NK）T细胞能选择性清除肝细胞癌（HCC）细胞系。在本研究中，我们探讨了经唑来膦酸扩增的HI γδ T细胞如何对HI NK抵抗的Huh7 HCC细胞表现出更优细胞毒效应的潜在机制。
γδ T细胞从活体肝移植供者或健康志愿者外周血单个核细胞（PBMC）中获得，并在IL-2、IL-15和唑来膦酸存在下扩增2周。通过乳酸脱氢酶（LDH）测定法在体外测量细胞毒性，并通过流式细胞术使用羧基荧光素琥珀酰亚胺酯（CFSE）在体内测量。
扩增的HI γδ T细胞对Huh7细胞的细胞毒性与Huh7细胞中焦磷酸表达高于SNU398细胞相关。相反，HI γδ T细胞对SNU398细胞的细胞毒性依赖于NKG2D。HI γδ T细胞表达的PD-1少于PB γδ T细胞。HI γδ T细胞对Du145和PC3前列腺癌细胞的细胞毒性也与这些细胞中的焦磷酸表达以及NKG2D和DNAM-1相关。
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.
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