Evidence map›Paper›PMID 42481445›Full record

ArticleCell death discovery2026

Cytokine-induced expandable memory NK cells with significant metabolic, epigenetic remodeling, and persistence properties.

Hongye Wang, Jingwei Tu, Yi Luo, Xinxin Yuan, Xin Fang, Zhengyi Lu, Li Han, Yongjia Xue, Wencheng Zhang, Qianggang Dong and 1 more

Abstract read
PubMed Publisher
In one paragraph

Article in Cell death discovery, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Hongye Wang *Institute for Regenerative Medicine, Medical Innovation Center and State Key Laboratory of Cardiology, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, 200123, China.
Jingwei Tu *Institute for Regenerative Medicine, Medical Innovation Center and State Key Laboratory of Cardiology, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, 200123, China.
Yi LuoShanghai iCELL Biotechnology Co., Ltd, Shanghai, 200335, China.
Xinxin YuanShanghai iCELL Biotechnology Co., Ltd, Shanghai, 200335, China.
Xin FangShanghai iCELL Biotechnology Co., Ltd, Shanghai, 200335, China.
Zhengyi LuShanghai iCELL Biotechnology Co., Ltd, Shanghai, 200335, China.
Li HanShanghai iCELL Biotechnology Co., Ltd, Shanghai, 200335, China.
Yongjia XueInstitute for Regenerative Medicine, Medical Innovation Center and State Key Laboratory of Cardiology, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, 200123, China.
Wencheng ZhangInstitute for Regenerative Medicine, Medical Innovation Center and State Key Laboratory of Cardiology, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, 200123, China. wencheng.v.zhang@outlook.com.ORCID http://orcid.org/0000-0003-2848-1611
Qianggang DongShanghai iCELL Biotechnology Co., Ltd, Shanghai, 200335, China. qgdong@icell.com.cn.ORCID http://orcid.org/0009-0000-2592-2106
Zhiying HeInstitute for Regenerative Medicine, Medical Innovation Center and State Key Laboratory of Cardiology, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, 200123, China. zyhe@tongji.edu.cn.ORCID http://orcid.org/0000-0002-8298-7835

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82300718National Natural Science Foundation of China (National Science Foundation of China) 82301904National Natural Science Foundation of China (National Science Foundation of China) 82401978
6 · The paper itself

Abstract

Recent investigations have indicated that NK cells induced overnight with IL-12/15/18 cytokines possess memory-like characteristics (refers as CIML NK, cytokine induced memory-like NK cells), demonstrating enhanced effector function and prolonged persistence. Preclinical studies and very early clinical trials revealed the promising clinical activity of CIML NK cells in the treatment of hematological malignancies, especially acute myelocytic leukemia (AML). However, the current manufacturing method for CIML NK cells do not endow these cells the ability to expand robustly ex vivo. The low production efficiency limits their clinical application. In this study, we established a novel expansion platform for generating memory-like NK cells by first inducing memory properties through stimulation with CD16a, IL-15, and IL-18, followed by a robust expansion phase. This method can effectively and stably expand healthy donor-derived Peripheral NK (PBNK) cells by more than 200-fold within two weeks, with a purity exceeding 95%. Importantly, these ex vivo expanded NK (ExNK) cells exhibited hypomethylated state in the CNS-1 region (Conserved Noncoding Sequence 1) of IFNG gene, stronger metabolic ability, and enhanced effector function when compared to CIML NK cells. Based on these features, we named these expanded NK cells but still possess memory-like characteristics as mExNK (memory-like expanded NK cells). Bulk mRNA-seq further uncovered a high similarity between mExNK and CIML NK cells, with both highly expressing genes being related to proliferation, metabolism, and memory. Mouse tumor models proved that the infused mExNK exhibited longer persistence in vivo and stronger effector functions. Taken together, the method described herein showed an enhanced expansion efficiency for human CIML NK cells and would facilitate their clinic applications in cancer therapy.

Identifiers

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.