Evidence map›Paper›PMID 40605065›Full record

ArticleJournal of experimental & clinical cancer research : CR2025

Elucidating the role of N-myristoylation in the excessive membrane localization of PD-L1 in hypoxic cancers and developing a novel NMT1 inhibitor for combination with immune checkpoint blockade therapy.

Haoming Zhao, Zhen Zhang, Chaojun Zhang, Hexin Ma, Qingqing Wan, Xinran Zhao, Xu Wang, Ming Yan, Haiyan Guo, Jianjun Zhang and 1 more

Erratum issuedAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. 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. Review
  3. Intracellular PD-L1: Functions, Regulation, and Therapeutic Implications.International journal of biological sciences · 2026
    Review
  4. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Haoming ZhaoDepartment of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, Shanghai, China.
Zhen ZhangDepartment of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, Shanghai, China.
Chaojun ZhangDepartment of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, Shanghai, China.
Hexin MaDepartment of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, Shanghai, China.
Qingqing WanDepartment of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, Shanghai, China.
Xinran ZhaoDepartment of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, Shanghai, China.
Xu WangDepartment of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, Shanghai, China.
Ming YanDepartment of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, Shanghai, China.
Haiyan GuoDepartment of Clinical Laboratory, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, Shanghai, China.
Jianjun ZhangDepartment of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, Shanghai, China. zjjbio@sjtu.edu.cn.
Wantao ChenDepartment of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, Shanghai, China. chenwantao196323@sjtu.edu.cn.

Funding

National Natural Science Foundation of China Key Projects 82230090
6 · The paper itself

Abstract

backgroundMost cancers, including head and neck squamous cell carcinoma (HNSCC), frequently exhibit an approximately 80% lack of response to immune checkpoint blockade (ICB) therapy, largely attributed to hypoxia-induced tumor immune suppression. Although hypoxia is known to upregulate PD-L1 expression, the key mechanisms by which it enhances PD-L1 membrane localization and high expression remain elusive.

methodsWe investigated the molecular mechanisms by which hypoxia enhances PD-L1 membrane localization in HNSCC cells. Additionally, we tested the efficacy of combining an anti-PD-1 antibody with the NMT1 inhibitor PCLX-001 in HNSCC xenograft mice and conducted a retrospective clinical study to assess NMT1 as a prognostic biomarker.

resultsOur study revealed that hypoxia-inducible factor-1α (HIF1α) upregulates N-myristoyltransferase 1 (NMT1), which mediates the myristoylation of calcineurin B homologous protein 1 (CHP1). Myristoylated CHP1 binds to PD-L1, facilitating its rapid translocation to the cell membrane and increasing PD-L1-mediated immune evasion. The NMT1 inhibitor low-dose PCLX-001 blocks CHP1 myristoylation, disrupting excessive PD-L1 membrane localization and attenuating cancer immune suppression. In HNSCC xenograft mice, administering an anti-PD-1 antibody combined with low-dose PCLX-001 via intratumoral injection significantly improved the treatment response rate and produced synergistic anticancer effects with no significant weight loss. Furthermore, our retrospective clinical study demonstrated that NMT1 protein levels can serve as an independent prognostic biomarker for HNSCC.

conclusionThese findings provide robust theoretical support for the translational application of combining NMT1 inhibitors and ICB therapy in cancers under hypoxic conditions. This study introduces a combined cancer therapy strategy named "spatial blockade plus signaling inhibition of PD-L1."

Indexed as

AcyltransferasesB7-H1 AntigenHead and Neck NeoplasmsImmune Checkpoint InhibitorsSquamous Cell Carcinoma of Head and NeckAnimalsCell Line, TumorCell MembraneFemaleHumansMaleMiceRetrospective StudiesXenograft Model Antitumor AssaysAcyltransferasesB7-H1 AntigenCD274 protein, humanImmune Checkpoint InhibitorsHypoxiaImmune checkpoint blockadeNMT1N-myristoylationPD-L1

Identifiers

PMID40605065
PMCPMC12219335

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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.