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CD69(+) Vδ1γδ T 细胞是肝细胞癌中的抗肿瘤亚群

英文原题:CD69(+) Vδ1γδ T cells are anti-tumor subpopulations in hepatocellular carcinoma.

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CD69(+) Vδ1γδ T cells are anti-tumor subpopulations in hepatocellular carcinoma.

PubMed 2024/06/24(内容时间) Mol Immunol Q2 · IF 3.7(JCR 2025)

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研究概要

CD69 + Vδ1γδ T 细胞是 HCC 患者中功能性的 Vδ1γδ T 细胞亚群。循环 CD69 + Vδ1γδ T 细胞是 HCC 免疫治疗中有前景的候选细胞。

研究思路结论见上方概要

肝细胞癌(HCC)是Vδ1γδ T细胞识别的应激配体广泛表达的恶性肿瘤之一,在γδ T细胞过继免疫治疗中备受关注。本研究旨在鉴定HCC中潜在的抗肿瘤Vδ1γδ T细胞亚群。

健康供者(HDs)和HCC患者从郑州大学附属肿瘤医院招募。分别获取血液和肿瘤组织样本。采用生物信息学方法分析总γδ T细胞及亚群浸润情况、Vδ1γδ T细胞高浸润和低浸润水平HCC患者的总生存期,以及TRDV1高/低CD69高/低组中IFNG、颗粒酶A、颗粒酶B和穿孔素的表达。采用免疫荧光检测HCC中CD69表达和Vδ1γδT细胞浸润。采用流式细胞术对血液和肿瘤组织样本中的Vδ1γδ T细胞进行表型分析。

浸润于HCC中的Vδ1γδ T细胞与更好的临床结局相关。对HCC肿瘤微环境(TME)的研究表明,与较小肿瘤体积相关的是CD69 + Vδ1γδ亚群浸润,而非总的Vδ1γδ T细胞。此外,同时具有高TRDV1和CD69表达的HCC患者产生更多效应分子,并且生存时间更长。由于肿瘤微环境中的Vδ1γδ T细胞通常难以获取,我们证明CD69 + Vδ1γδ T细胞也存在于HCC患者的外周血单个核细胞(PBMC)中,并且比HDs表现出增强的细胞毒性潜能。最后,我们研究了其功能,发现CD69 + Vδ1γδ T细胞在受到肿瘤细胞刺激时表现出更强的肿瘤反应性。

展开英文摘要原文

Healthy donors (HDs) and HCC patients were recruited from the Affiliated Cancer Hospital of Zhengzhou University. Blood and tumor tissue samples were obtained respectively. Bioinformatics methods were used to analyze total γδ T cells and subsets infiltration, overall survival of HCC patients with high and low infiltration level of Vδ1γδ T cells, and IFNG, granzyme A, granzyme B and perforin expression in TRDV1 high/low CD69 high/low groups. CD69 expression and Vδ1γδT cells infiltration in HCC were detected by immunofluorescence. Phenotypic analysis of Vδ1γδ T cells in blood and tumor tissue samples were performed by flow cytometry.

Vδ1γδ T cells infiltrating in HCC were associated with better clinical outcome. Study in tumor micro-environment (TME) of HCC demonstrated that not total Vδ1γδ T but CD69 + Vδ1γδ subset infiltration was associated with smaller tumor volume. Moreover, HCC patients simultaneously with high TRDV1 and CD69 expression produced more effector molecules and had longer survival time. Since Vδ1γδ T cells in the tumor microenvironment were often difficult to access, we demonstrated that CD69 + Vδ1γδ T cells also existed in peripheral blood mononuclear cells (PBMC) of HCC and displayed enhanced cytotoxic potentials than HDs. Finally, we investigated the functions and found that CD69 + Vδ1γδ T cells exhibited stronger tumor reactivities when challenged by tumor cells.

CD69 + Vδ1γδ T cells are functional Vδ1γδ T cell subsets in patients with HCC. Circulating CD69 + Vδ1γδ T cell is a promising candidate in immunotherapy of HCC.

论文信息

作者
You H、Wang Y、Wang X、Zhu H、Zhao Y、Qin P、Liu X、Zhang M
第一作者单位
Department of Immunotherapy, the Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou 450008, China.China
通讯作者单位
Department of Immunotherapy, the Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou 450008, China. Electronic address: zlyygql0855@zzu.edu.cn.China
期刊
Molecular immunology2024 Aug
原文标识
PubMed 38917598 · DOI 10.1016/j.molimm.2024.06.006