Evidence mapPaperPMID 40959272Full record

ArticleInternational journal of biological sciences2025

Overcoming Ferroptosis-Induced Exhaustion of NK Cells through Inhibition of the ATF3-Mediated Integrated Stress Response in Ovarian Cancer.

Tian Chen, Shulin Zhou, Yashuang Zhang, Huangyang Meng, Huixian Miao, Mingming Feng, Yi Jiang, Yicong Wan, Lin Zhang, Wenjun Cheng

Abstract read
In one paragraph

Article in International journal of biological sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Review
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

10 authors.

Tian ChenDepartment of Gynecology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China.
Shulin ZhouDepartment of Gynecology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China.
Yashuang ZhangDepartment of Gynecology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China.
Huangyang MengDepartment of Gynecology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China.
Huixian MiaoDepartment of Gynecology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China.
Mingming FengDepartment of Gynecology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China.
Yi JiangDepartment of Gynecology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China.
Yicong WanDepartment of Gynecology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China.
Lin ZhangDepartment of Gynecology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China.
Wenjun ChengDepartment of Gynecology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The absence of cytotoxic effector cells, such as CD8⁺ T cells or Natural Killer (NK) cells, within tumors establishes an immune-cold tumor microenvironment (TME), contributing to poor immunotherapy responses, as observed in ovarian cancer. Although prior studies implicate NK cell exhaustion within the TME related to ferroptosis, the underlying mechanisms remain undefined. This study demonstrates that upon infiltrating the ovarian cancer TME, NK cells activate an integrated stress response (ISR) centered on ATF3. This ATF3-mediated ISR suppresses NRF2 expression, compromising their ability to counteract oxidative stress and ultimately triggering ferroptosis. Critically, we show that co-treatment with the ISR inhibitor ISRIB and NK cells not only prevents NK cell ferroptosis but also synergizes to enhance tumor cell killing. These findings provide novel insights into the mechanisms driving NK cell exhaustion within the TME and identify ISR inhibition as a promising therapeutic target and intervention strategy for developing NK cell-based therapies against ovarian cancer.

Indexed as

Activating Transcription Factor 3FerroptosisKiller Cells, NaturalOvarian NeoplasmsAnimalsCell Line, TumorFemaleHumansNF-E2-Related Factor 2Oxidative StressTumor MicroenvironmentActivating Transcription Factor 3ATF3 protein, humanNF-E2-Related Factor 2ferroptosisintegrated stress responseNK cellNRF2ovarian cancertumor microenvironment

Identifiers

PMID40959272
PMCPMC12435575

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.