Activated but impaired IFN-γ production of mucosal-associated invariant T cells in patients with hepatocellular carcinoma.
Activated but impaired IFN-γ production of mucosal-associated invariant T cells in patients with hepatocellular carcinoma.
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肝细胞癌患者粘膜相关不变 T 细胞的 IFN-γ 生成被激活但受损
DOI：
10.1136/jitc-2021-003685
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发表时间：
2021-11
影响因子：
10.9
通讯作者：
Gao Y
中科院分区：
文献类型：
--
作者：
Huang W;Ye D;He W;He X;Shi X;Gao Y
目的 粘膜相关不变 T (MAIT) 细胞是具有免疫调节活性的先天性 T 细胞，最近发现与多种肿瘤类型相关。窦内 MAIT 细胞在肝细胞癌 (HCC) 中的作用尚未得到充分表征。设计 外周血样本取自 HCC 患者和健康对照。肝相关单核细胞（LMC）是从供体和接受肝移植的 HCC 患者的肝脏灌注中收集的。通过流式细胞术分析 HCC 患者的血液和肝脏灌注液中的 CD3 + CD161 + Vα7.2 + MAIT 细胞频率、表型和功能。结果 HCC患者外周血和肝脏中MAIT细胞数量少于健康对照者。这些细胞产生的干扰素-γ (IFN-γ) 也减少了。外周MAIT细胞显示HLA-DR（人类白细胞抗原DR）和抑制分子PD-1（程序性细胞死亡蛋白1）上调，但窦内MAIT细胞上调没有发现显着差异。相对于HCC患者的外周血，MAIT细胞在肝脏中显着富集。高水平的激活标记物和耗竭标记物，包括 在 HCC 患者的 LMC 中观察到 HLA-DR、CD69 和 PD-1，但在外周血中未观察到。单细胞 RNA 测序显示，肝细胞癌患者和对照组的窦内 MAIT 细胞表现出不同的特征。结论 我们的研究表明 MAIT 细胞的改变与 HCC 相关。 HCC 患者外周血和肝脏中 MAIT 细胞的独特活性和功能可能表明其潜在作用 这些细胞在疾病发病机制中的作用。
Objective Mucosal-associated invariant T (MAIT) cells are innate T cells with immunoregulatory activity and were recently found to be associated with various tumor types. The role of intrasinusoidal MAIT cells in hepatocellular carcinoma (HCC) has not been fully characterized. Design Peripheral blood samples were obtained from patients with HCC and healthy controls. Liver-associated mononuclear cells (LMCs) were collected from liver perfusions of donors and patients with HCC undergoing liver transplantation. Blood and liver perfusates from patients with HCC were analyzed by flow cytometry for CD3 +CD161+Vα7.2+MAIT cell frequency, phenotype, and function. Results There were fewer MAIT cells in the peripheral blood and liver of patients with HCC than in the healthy controls. Interferon-γ (IFN-γ) production by these cells was also reduced. Peripheral MAIT cells showed upregulation of HLA-DR (Human Leukocyte Antigen DR） and the inhibitory molecule PD-1 (Programmed Cell Death Protein 1), but no significant differences in upregulation were found in intrasinusoidal MAIT cells. MAIT cells were significantly enriched in the liver relative to that in the peripheral blood of patients with HCC. High levels of activation markers and exhaustion markers including HLA-DR, CD69, and PD-1 were observed in LMCs of patients with HCC but not in the peripheral blood. Single-cell RNA sequencing revealed that intrasinusoidal MAIT cells exhibited distinct features in patients with HCC and the controls. Conclusion Our study showed that alterations in MAIT cells are associated with HCC. The distinct activity and function of MAIT cells in the peripheral blood and liver of patients with HCC might suggest a potential role of these cells in disease pathogenesis.
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影响因子：
3.7
作者：
Raziorrouh B;Heeg M;Kurktschiev P;Schraut W;Zachoval R;Wendtner C;Wächtler M;Spannagl M;Denk G;Ulsenheimer A;Bengsch B;Pircher H;Diepolder HM;Grüner NH;Jung MC
通讯作者：
Jung MC
影响因子：
29.4
作者：
El-Serag HB
通讯作者：
El-Serag HB
影响因子：
30.5
作者：
Le Bourhis, Lionel;Martin, Emmanuel;Lantz, Olivier
通讯作者：
Lantz, Olivier
影响因子：
7.3
作者：
Juno JA;Waruk JLM;Wragg KM;Mesa C;Lopez C;Bueti J;Kent SJ;Ball TB;Kiazyk SA
通讯作者：
Kiazyk SA
慢性 HBV 感染者中粘膜相关的不变 T 细胞严重减少并耗尽
影响因子：
2.5
作者：
Huang, Wenyong;He, Wenjing;Gao, Yifang
通讯作者：
Gao, Yifang