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卵巢癌中 γδ T 细胞 TIGIT、PD-1、TIM-3 与 CD39 的组织特异性表达

英文原题:Tissue-Specific Expression of TIGIT, PD-1, TIM-3, and CD39 by γδ T Cells in Ovarian Cancer.

PubMed 2022/03/11(内容时间) Cells Q2 · IF 6(JCR 2025)

研究概要

V1T细胞群体在OvCA患者的MALs和原发肿瘤中显示出高流行率。

中文摘要

卵巢癌(OvCA)患者MALs(恶性腹水淋巴细胞)、TILs(TIL(肿瘤浸润淋巴细胞)和PBLs(外周血淋巴细胞)中T细胞的表型特征研究尚缺乏。因此,我们对n = 18例OvCA患者的MAL、TIL和PBL标本以及年龄匹配的健康供者(HD,n = 14)的PBL中的T细胞丰度进行了定量分析。采用多色流式细胞术评估T细胞亚群上抑制性受体(TIGIT、PD-1和TIM-3)、刺激性受体(Ox40)以及嘌呤能外切酶(CD39和CD73)的表达。我们发现在MALs和TILs中存在V 1 T细胞的丰富浸润。这些细胞在分化程度上存在差异:大多数V 1 TILs呈现效应记忆(EM)表型,而V 1 MALs则具有更成熟的终末分化效应记忆细胞(TEMRA)表型,CD45RA高表达。TIGIT和TIM-3在MALs和PBLs中均大量表达,而V 1 TILs表现出最高水平的PD-1、CD39和Ox40。我们还观察到所分析分子在成熟分化阶段上的特异性聚类。关于共表达,与MALs和PBLs相比,V 1 TILs中同时表达TIGIT与PD-1或CD39的细胞水平最高。总之,V 1 T细胞群体在OvCA患者的MALs和原发肿瘤中呈现高丰度。由于其(共)表达可靶向的免疫受体,特别是TILs中TIGIT与PD-1和CD39的共表达,基于V 1 T细胞的方法联合这些靶点的抑制可能代表一种有前景的OvCA治疗策略。

展开英文摘要原文

Phenotypic characterization of T cells in the MALs (malignant ascites lymphocytes), TILs (tumor infiltrating lymphocytes), and PBLs (peripheral blood lymphocytes) of ovarian cancer (OvCA) patients is lacking. Therefore, we quantified T cell prevalence in MAL, TIL, and PBL specimens from n = 18 OvCA patients and PBL from age-matched healthy donors (HD, n = 14). Multicolor flow cytometry was performed to evaluate the expression of inhibitory receptors (TIGIT, PD-1 and TIM-3), stimulatory receptors (Ox40), and purinergic ectoenzymes (CD39 and CD73) on T cell subsets. We identified an abundant infiltration of V 1 T cells in the MALs and TILs. These cells varied in their differentiation: The majority of V 1 TILs displayed an effector memory (EM) phenotype, whereas V 1 MALs had a more mature phenotype of terminally differentiated effector memory cells (TEMRA) with high CD45RA expression. TIGIT and TIM-3 were abundantly expressed in both MALs and PBLs, whereas V 1 TILs exhibited the highest levels of PD-1, CD39, and Ox40. We also observed specific clusters on mature differentiation stages for the analyzed molecules. Regarding co-expression, V 1 TILs showed the highest levels of cells co-expressing TIGIT with PD-1 or CD39 compared to MALs and PBLs. In conclusion, the V 1 T cell population showed a high prevalence in the MALs and primary tumors of OvCA patients. Due to their (co-)expression of targetable immune receptors, in particular TIGIT with PD-1 and CD39 in TILs, V 1 T cell-based approaches combined with the inhibition of these targets might represent a promising strategy for OvCA.

论文信息

作者
Weimer P、Wellbrock J、Sturmheit T、Oliveira-Ferrer L、Ding Y、Menzel S、Witt M、Hell L
单位
Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald University Cancer Center, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.Germany
文献类型
非美国政府资助研究
期刊
Cells2022 Mar 11
原文标识
PubMed 35326415 · DOI 10.3390/cells11060964