Evidence map›Paper›PMID 40341398›Full record

ArticleNature communications2025

Palmitoylation prevents B7-H4 lysosomal degradation sustaining tumor immune evasion.

Yijian Yan, Jiali Yu, Weichao Wang, Ying Xu, Kole Tison, Rongxin Xiao, Sara Grove, Shuang Wei, Linda Vatan, Max Wicha and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing 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

27 citing papers in PubMed.

  1. Article
  2. CD112 Lactylation Drives Dual Immune Evasion From CD8+ T Cells and NK Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  3. Article
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  20. The Roles of ProteinCancer communications (London, England) · 2026
    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

12 authors.

Yijian Yan *Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA.
Jiali Yu *Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA.
Weichao WangDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA.
Ying XuDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA.
Kole TisonDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-4076-6380
Rongxin XiaoDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA.
Sara GroveDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA.
Shuang WeiDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA.
Linda VatanDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA.
Max WichaDepartment of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0003-4180-7727
Ilona KryczekDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-3130-2533
Weiping ZouDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA. wzou@umich.edu.ORCID http://orcid.org/0000-0001-7952-3549

Funding

U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) CA123088U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) CA152470U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) CA193136U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) CA217648U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) CA46592
6 · The paper itself

Abstract

B7-H4 functions as an immune checkpoint in the tumor microenvironment (TME). However, the post-translational modification (PTM) of B7-H4 and its translational potential in cancer remains incompletely understood. We find that ZDHHC3, a zinc finger DHHC-type palmitoyltransferase, palmitoylates B7-H4 at Cys130 in breast cancer cells, preventing its lysosomal degradation and sustaining B7-H4-mediated immunosuppression. Knockdown of ZDHHC3 in tumors results in robust anti-tumor immunity and reduces tumor progression in murine models. Moreover, abemaciclib, a CDK4/6 inhibitor, primes lysosome activation and promotes lysosomal degradation of B7-H4 independently of the tumor cell cycle. Treatment with abemaciclib results in T cell activation and mitigates B7-H4-mediated immune suppression via inducing B7-H4 degradation in preclinical tumor models. Thus, B7-H4 palmitoylation is an important PTM controlling B7-H4 protein stability and abemaciclib may be repurposed to promote B7-H4 degradation, thereby treating patients with B7-H4 expressing tumors.

Indexed as

Breast NeoplasmsLipoylationLysosomesTumor EscapeV-Set Domain-Containing T-Cell Activation Inhibitor 1AcyltransferasesAminopyridinesAnimalsBenzimidazolesCell Line, TumorFemaleHumansLymphocyte ActivationMiceProteolysisT-LymphocytesabemaciclibAcyltransferasesAminopyridinesBenzimidazolesV-Set Domain-Containing T-Cell Activation Inhibitor 1VTCN1 protein, human

Identifiers

PMID40341398
PMCPMC12062253

What OpenQuestion holds

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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.