Evidence map›Paper›PMID 42508829›Full record

ArticleJournal for immunotherapy of cancer2026

Targeting TOMM40 unleashes immunogenic mitophagy to facilitate antigen presentation and immunotherapy sensitization.

Zhiwei Zhang, Yu-An Xie, Chenglin Mu, Shiying Sheng, Jinyuan Zhang, Jie Han, Jiwen Li, Zhengfu He, Xia Liu

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal for immunotherapy of cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

9 authors.

Zhiwei ZhangDepartment of Cardiac Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.ORCID http://orcid.org/0009-0005-0739-852X
Yu-An XieZhejiang Key Laboratory of Intelligent Manufacturing for Functional Chemicals, ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou, Zhejiang, China.ORCID http://orcid.org/0009-0008-7569-1383
Chenglin MuZhejiang Key Laboratory of Intelligent Manufacturing for Functional Chemicals, ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou, Zhejiang, China.ORCID http://orcid.org/0009-0007-6326-7190
Shiying ShengDepartment of Critical Care Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.ORCID http://orcid.org/0009-0008-7801-0539
Jinyuan ZhangZhejiang Key Laboratory of Intelligent Manufacturing for Functional Chemicals, ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou, Zhejiang, China.ORCID http://orcid.org/0009-0004-5277-7054
Jie HanDepartment of Cardiac Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.ORCID http://orcid.org/0009-0001-0649-2638
Jiwen LiDepartment of Cardiac Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China xia.liu@zju.edu.cn hezhengfu@zju.edu.cn lijiwen@zju.edu.cn.ORCID http://orcid.org/0000-0002-8595-860X
Zhengfu HeDepartment of Thoracic Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China xia.liu@zju.edu.cn hezhengfu@zju.edu.cn lijiwen@zju.edu.cn.ORCID http://orcid.org/0000-0002-6747-7490
Xia LiuDepartment of Cardiac Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China xia.liu@zju.edu.cn hezhengfu@zju.edu.cn lijiwen@zju.edu.cn.ORCID http://orcid.org/0000-0002-8062-757X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMitophagy is a mitochondrial quality control process that maintains cellular homeostasis in cancer, yet whether its dysregulation can be exploited to induce tumor immunogenicity remains unclear.

methodsWe integrated pancancer single-cell transcriptomic analyses with genetic perturbation strategies in hepatocellular carcinoma models, including CRISPR/Cas9-mediated gene depletion, in vivo syngeneic tumor systems, and RNA-based lipid nanoparticle delivery. Mechanistic investigations combined mitochondrial functional assays, imaging-based mitophagy analysis, flow cytometry, and transcriptional profiling, together with evaluation of immune checkpoint blockade responses in preclinical and clinical cohorts.

resultsWe identify translocase of the outer mitochondrial membrane 40 (TOMM40) as a mitochondrial import gatekeeper that restrains PINK1-Parkin-dependent mitophagy. Loss of TOMM40 induces catastrophic mitochondrial dysfunction and triggers a lethal form of hyperactivated mitophagy. This process is immunogenic and converts immune-cold tumors into immune-inflamed states characterized by enhanced CD8

conclusionsTOMM40 functions as a mitochondrial immune checkpoint that controls the threshold of immunogenic mitophagy. Its loss reprograms mitochondrial stress into antigen presentation and immune activation, providing a strategy to convert immune-cold tumors into immune-responsive states.

Indexed as

Antigen PresentationImmunotherapyMitochondrial Precursor Protein Import Complex ProteinsMitophagyAnimalsHumansMiceMitochondriaMitochondrial Precursor Protein Import Complex ProteinsTOMM40 protein, humanAntigen PresentationImmunotherapyMitochondria

Identifiers

PMID42508829
PMCPMC13409098

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Registered trials

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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.