Evidence map›Paper›PMID 41542770›Full record

ArticleThe Journal of clinical investigation2026

Targeting the N-acetyltransferase 10/DKK2 axis enhances CD8+ T cell antitumor activity in colorectal cancer models.

Mengmeng Li, Xiaoya Zhao, Jun Wu, Shimeng Zhou, Yao Fu, Chen Chen, Zhuang Ma, Jiawen Xu, Yun Qian, Zhangding Wang and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical investigation, 2026. 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. Article
  2. Review
  3. Review
  4. Functional roles and mechanisms of NAT10-mediated RNA acFrontiers in cell and developmental biology · 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

19 authors.

Mengmeng LiDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Anhui Medical University, MOE Innovation Center for Basic Research in Tumor Immunotherapy, Anhui Province Key Laboratory of Tumor Immune Microenvironment and Immunotherapy, Hefei, Anhui Province, China.
Xiaoya ZhaoMedical School of Nanjing University, Nanjing, Jiangsu Province, China.
Jun WuDepartment of Thoracic Surgery, Northern Jiangsu People's Hospital, Yangzhou, China.
Shimeng ZhouMedical School of Nanjing University, Nanjing, Jiangsu Province, China.
Yao FuDepartment of Pathology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China.
Chen ChenDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Anhui Medical University, MOE Innovation Center for Basic Research in Tumor Immunotherapy, Anhui Province Key Laboratory of Tumor Immune Microenvironment and Immunotherapy, Hefei, Anhui Province, China.
Zhuang MaMedical School of Nanjing University, Nanjing, Jiangsu Province, China.
Jiawen XuMedical School of Nanjing University, Nanjing, Jiangsu Province, China.
Yun QianMedical School of Nanjing University, Nanjing, Jiangsu Province, China.
Zhangding WangDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Anhui Medical University, MOE Innovation Center for Basic Research in Tumor Immunotherapy, Anhui Province Key Laboratory of Tumor Immune Microenvironment and Immunotherapy, Hefei, Anhui Province, China.
Bo WangDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Anhui Medical University, MOE Innovation Center for Basic Research in Tumor Immunotherapy, Anhui Province Key Laboratory of Tumor Immune Microenvironment and Immunotherapy, Hefei, Anhui Province, China.
Qiang WangDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Anhui Medical University, MOE Innovation Center for Basic Research in Tumor Immunotherapy, Anhui Province Key Laboratory of Tumor Immune Microenvironment and Immunotherapy, Hefei, Anhui Province, China.
Qingqing DingDepartment of Geriatric Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
Changyu ChenDepartment of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China.
Honggang WangDepartment of Gastroenterology, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu Province, China.
Xiaozhong YangDepartment of Gastroenterology, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu Province, China.
Weijie DaiDepartment of Gastroenterology, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu Province, China.
Wenjie ZhangDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Anhui Medical University, MOE Innovation Center for Basic Research in Tumor Immunotherapy, Anhui Province Key Laboratory of Tumor Immune Microenvironment and Immunotherapy, Hefei, Anhui Province, China.
Shouyu WangDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Anhui Medical University, MOE Innovation Center for Basic Research in Tumor Immunotherapy, Anhui Province Key Laboratory of Tumor Immune Microenvironment and Immunotherapy, Hefei, Anhui Province, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Despite overexpression of N-acetyltransferase 10 (NAT10) in colorectal cancer (CRC), its immunomodulatory role in the tumor microenvironment remains elusive. Here, we reveal that NAT10 promotes immune evasion through N4-acetylcytosine-dependent (ac4C-dependent) mRNA stabilization. Using syngeneic mouse models (MC38/CT-26), intestinal epithelial-cell specific Nat10 conditional KO (Nat10cKO) mice, patient-derived organoids, and clinical specimens, we show that Nat10 ablation enhanced CD8+ T cell-mediated antitumor immunity. Single-cell RNA-seq revealed increased cytotoxic CD8+ T cell infiltration in Nat10cKO tumors, which was corroborated by the inverse correlation of tumoral NAT10 expression and CD8+ T cell number in clinical specimens. Multi-omics integration analysis identified DKK2 as the predominant NAT10-regulated transcript. NAT10 stabilized DKK2 mRNA via ac4C modification, leading to high expression of the DKK2 protein. Secreted DKK2 engaged LRP6 receptors to activate AKT-mTOR signaling, inducing cholesterol accumulation in CD8+ T cells and impairing their cytotoxicity. Pharmacological NAT10 inhibition (Remodelin treatment) or DKK2 neutralization restored CD8+ T cell function and synergized with anti-PD-1 therapy. Our findings establish the NAT10/DKK2/LRP6/AKT-mTOR/cholesterol axis as a critical regulator of CD8+ T cell dysfunction in CRC, positioning NAT10/DKK2 as a potential target to enhance immunotherapy efficacy.

Indexed as

AcetyltransferasesCD8-Positive T-LymphocytesColorectal NeoplasmsNeoplasm ProteinsNeoplasms, ExperimentalAnimalsHumansMiceMice, KnockoutSignal TransductionAcetyltransferasesNeoplasm ProteinsCancer immunotherapyColorectal cancerEpigeneticsGastroenterologyImmunologyOncology

Identifiers

PMID41542770
PMCPMC12807479

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.