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》。
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
Immunity:《免疫》,创刊于1994年。隶属于细胞出版社,最新if:21.522
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