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抑制转录因子HIF-1α能够增强NK细胞活性
作者:小柯机器人 发布时间:2020/5/25 21:19:58

德国海德堡大学Adelheid Cerwenka课题组利用单细胞RNA测序发现,抑制转录因子HIF-1α能够增强NK细胞活性。该研究于2020年5月22日在线发表于《免疫》。

研究人员通过使用单细胞RNA测序定义了小鼠肿瘤浸润性自然杀伤(NK)细胞的转录图谱。NK细胞中Hif1a的条件缺失导致肿瘤浸润NK细胞中肿瘤生长减少,激活标志物、效应分子的表达升高以及NF-κB途径的富集。NF-κB激活和Hif1a-/-NK细胞增强的抗肿瘤活性需要髓样细胞的白介素18(IL-18)。
 
利用HIF-1α抑制剂进行扩增培养可增强人类NK细胞的反应。HIF1A的低表达与人肿瘤浸润NK细胞中IFNG的高表达有关,实体瘤中丰富的NK-IL18-IFNG标记与患者总体生存期增加相关。因此,抑制HIF-1α可释放NK细胞的抗肿瘤活性,从而用于癌症治疗。
 
据介绍,增强肿瘤中免疫细胞的功能仍然是癌症免疫疗法的主要难题。缺氧是实体瘤的常见特征,细胞可通过上调转录因子HIF-1α来适应。
 
附:英文原文

Title: Single-Cell RNA Sequencing of Tumor-Infiltrating NK Cells Reveals that Inhibition of Transcription Factor HIF-1α Unleashes NK Cell Activity

Author: Jing Ni, Xi Wang, Ana Stojanovic, Qin Zhang, Marian Wincher, Lea Bühler, Annette Arnold, Margareta P. Correia, Manuel Winkler, Philipp-Sebastian Koch, Veronika Sexl, Thomas Hfer, Adelheid Cerwenka

Issue&Volume: 2020-05-22

Abstract: Enhancing immune cell functions in tumors remains a major challenge in cancer immunotherapy.Hypoxia is a common feature of solid tumors, and cells adapt by upregulating the transcriptionfactor HIF-1α. Here, we defined the transcriptional landscape of mouse tumor-infiltratingnatural killer (NK) cells by using single-cell RNA sequencing. Conditional deletionof Hif1a in NK cells resulted in reduced tumor growth, elevated expression of activation markers,effector molecules, and an enriched NF-κB pathway in tumor-infiltrating NK cells.Interleukin-18 (IL-18) from myeloid cells was required for NF-κB activation and theenhanced anti-tumor activity of Hif1a/ NK cells. Extended culture with an HIF-1α inhibitor increased human NK cell responses.Low HIF1A expression was associated with high expression of IFNG in human tumor-infiltrating NK cells, and an enriched NK-IL18-IFNG signature in solid tumors correlated with increased overall patient survival. Thus,inhibition of HIF-1α unleashes NK cell anti-tumor activity and could be exploitedfor cancer therapy.

DOI: 10.1016/j.immuni.2020.05.001

Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30182-5

期刊信息

Immunity:《免疫》,创刊于1994年。隶属于细胞出版社,最新if:21.522
官方网址:https://www.cell.com/immunity/home
投稿链接:https://www.editorialmanager.com/immunity/default.aspx