Evidence map›Paper›PMID 40166933›Full record

ArticleThe Journal of clinical investigation2025

ACAT1 regulates tertiary lymphoid structures and correlates with immunotherapy response in non-small cell lung cancer.

Mengxia Jiao, Yifan Guo, Hongyu Zhang, Haoyu Wen, Peng Chen, Zhiqiang Wang, Baichao Yu, Kameina Zhuma, Yuchen Zhang, Jingbo Qie and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing 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

13 citing papers in PubMed.

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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

21 authors.

Mengxia JiaoShanghai Fifth People's Hospital, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Yifan GuoDepartment of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Hongyu ZhangDepartment of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Haoyu WenDepartment of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Peng ChenShanghai Fifth People's Hospital, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Zhiqiang WangShanghai Fifth People's Hospital, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Baichao YuDepartment of Immunology, School of Basic Medical Sciences, and MOE Innovative Center for New Drug Development of Immune Inflammatory Diseases, Fudan University, Shanghai, China.
Kameina ZhumaDepartment of Immunology, School of Basic Medical Sciences, and MOE Innovative Center for New Drug Development of Immune Inflammatory Diseases, Fudan University, Shanghai, China.
Yuchen ZhangDepartment of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Jingbo QieShanghai Fifth People's Hospital, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Yun XingShanghai Fifth People's Hospital, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Pengyuan ZhaoShanghai Fifth People's Hospital, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Zihe PanShanghai Fifth People's Hospital, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Luman WangDepartment of Immunology, School of Basic Medical Sciences, and MOE Innovative Center for New Drug Development of Immune Inflammatory Diseases, Fudan University, Shanghai, China.
Dan ZhangShanghai Fifth People's Hospital, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Fei LiDepartment of Pathology and Frontier Innovation Center, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Yijiu RenDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
Chang ChenDepartment of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
Yiwei ChuShanghai Fifth People's Hospital, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Jie GuDepartment of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Ronghua LiuShanghai Fifth People's Hospital, and Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Tertiary lymphoid structures (TLS) in the tumor microenvironment (TME) are emerging solid-tumor indicators of prognosis and response to immunotherapy. Considering that tumorigenesis requires metabolic reprogramming and subsequent TME remodeling, the discovery of TLS metabolic regulators is expected to produce immunotherapeutic targets. To identify such metabolic regulators, we constructed a metabolism-focused sgRNA library and performed an in vivo CRISPR screening in an orthotopic lung tumor mouse model. Combined with The Cancer Genome Atlas database analysis of TLS-related metabolic hub genes, we found that the loss of Acat1 in tumor cells sensitized tumors to anti-PD1 treatment, accompanied by increased TLS in the TME. Mechanistic studies revealed that ACAT1 resulted in mitochondrial protein hypersuccinylation in lung tumor cells and subsequently enhanced mitochondrial oxidative metabolism, which impeded TLS formation. Elimination of ROS by NAC or Acat1 knockdown promoted B cell aggregation and TLS construction. Consistently, data from tissue microassays of 305 patients with lung cancer showed that TLS were more abundant in non-small cell lung cancer (NSCLC) tissues with lower ACAT1 expression. Intratumoral ACAT1 expression was associated with poor immunotherapy outcomes in patients with NSCLC. In conclusion, our results identified ACAT1 as a metabolic regulator of TLS and a promising immunotherapeutic target in NSCLC.

Indexed as

Acetyl-CoA C-AcetyltransferaseCarcinoma, Non-Small-Cell LungImmunotherapyLung NeoplasmsNeoplasm ProteinsTertiary Lymphoid StructuresTumor MicroenvironmentAnimalsCell Line, TumorFemaleHumansMaleMiceACAT1 protein, humanAcetyl-CoA C-AcetyltransferaseNeoplasm ProteinsCancer immunotherapyCarbohydrate metabolismCell stressImmunologyOncology

Identifiers

PMID40166933
PMCPMC11957694

What OpenQuestion holds

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LicenceCC BY
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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.