Evidence map›Paper›PMID 38489266›Full record

ArticleCell reports2024

PAD4 controls tumor immunity via restraining the MHC class II machinery in macrophages.

Michael R Pitter, Ilona Kryczek, Hongjuan Zhang, Nisha Nagarsheth, Houjun Xia, Zhenyu Wu, Yuzi Tian, Karolina Okla, Peng Liao, Weichao Wang and 8 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
6.3field-weighted citation impact, top 3% of its field
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

21 citing papers in PubMed, 26 citations in OpenAlex.

  1. Review
  2. Article
  3. CIITA/PRMT5 promote CD4BMC medicine · 2026
    Article
  4. Review
  5. Role of histone modifications in gastric cancer (Review).International journal of oncology · 2026
    Review
  6. Article
  7. Article
  8. Cell-Free DNA-Based Theranostics for Inflammatory Disorders.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  9. Article
  10. Review
  11. Review
  12. Review
  13. Integrative and deep learning-based prediction of therapy response in ovarian cancer.Journal of experimental & clinical cancer research : CR · 2025
    Article
  14. Article
  15. Article
  16. Citrullination in tumor immunity and therapy.The Journal of clinical investigation · 2025
    Review
  17. Article
  18. Article
  19. Review
  20. 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

18 authors at 1 institution in 1 country.

Michael R PitterDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA; Graduate Program in Molecular and Cellular Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
Ilona KryczekDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Hongjuan ZhangDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Nisha NagarshethDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Houjun XiaDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Zhenyu WuDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA.
Yuzi TianDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA.
Karolina OklaDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Peng LiaoDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Weichao WangDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Jiajia ZhouDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Gaopeng LiDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Heng LinDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Linda VatanDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Sara GroveDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Shuang WeiDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Yongqing LiDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA.
Weiping ZouDepartment of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA; Center of Excellence for Cancer Immunology and Immunotherapy, Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA; Graduate Programs in Immunology and Cancer Biology, University of Michigan Medical School, Ann Arbor, MI, USA. Electronic address: wzou@umich.edu.
University of Michigan–Ann Arbor · US

Funding

XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Alexey I Nesvizhskii · 1988 to 2026
$178.2M
CTL-killing capacity and cancer stiffness in cancer immunity and therapyR01CA261985 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WEIPING ZOU · 2022 to 2026
$3.2M
Regulatory T cells in cancer therapyR01CA244827 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ZOU, WEIPING · 2021 to 2025
$3.2M
Metabolic impact on T cell-mediated cancer immunity and therapyR01CA248430 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ZOU, WEIPING · 2020 to 2024
$3.2M
MDSCs in Ovarian CancerR01CA193136 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ZOU, WEIPING · 2015 to 2019
$2.5M
PAD2 and CitH3 in Pathogenesis of Sepsis-induced ALIR01HL155116 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ALAM, HASAN B, LI, YONGQING · 2021 to 2024
$2.1M
Memory T Cells in the Tumor MicroenvironmentR01CA152470 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ZOU, WEIPING · 2011 to 2015
$1.9M
Human Tregs in Ovarian CancerR01CA099985 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ZOU, WEIPING · 2006 to 2014
$1.8M
Novel immunosupressive macrophages in human ovarian tumorR01CA123088 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ZOU, WEIPING · 2007 to 2011
$1.4M
NCI NIH HHS P30 CA046592NCI NIH HHS R01 CA099985NCI NIH HHS R01 CA123088NCI NIH HHS R01 CA152470NCI NIH HHS R01 CA193136NCI NIH HHS R01 CA244827NCI NIH HHS R01 CA248430NCI NIH HHS R01 CA261985NHLBI NIH HHS R01 HL155116
6 · The paper itself

Abstract

Tumor-associated macrophages (TAMs) shape tumor immunity and therapeutic efficacy. However, it is poorly understood whether and how post-translational modifications (PTMs) intrinsically affect the phenotype and function of TAMs. Here, we reveal that peptidylarginine deiminase 4 (PAD4) exhibits the highest expression among common PTM enzymes in TAMs and negatively correlates with the clinical response to immune checkpoint blockade. Genetic and pharmacological inhibition of PAD4 in macrophages prevents tumor progression in tumor-bearing mouse models, accompanied by an increase in macrophage major histocompatibility complex (MHC) class II expression and T cell effector function. Mechanistically, PAD4 citrullinates STAT1 at arginine 121, thereby promoting the interaction between STAT1 and protein inhibitor of activated STAT1 (PIAS1), and the loss of PAD4 abolishes this interaction, ablating the inhibitory role of PIAS1 in the expression of MHC class II machinery in macrophages and enhancing T cell activation. Thus, the PAD4-STAT1-PIAS1 axis is an immune restriction mechanism in macrophages and may serve as a cancer immunotherapy target.

Indexed as

HydrolasesProtein Processing, Post-TranslationalAnimalsHistocompatibility Antigens Class IIMacrophagesMiceProtein-Arginine DeiminasesProtein-Arginine Deiminase Type 4Histocompatibility Antigens Class IIHydrolasesProtein-Arginine DeiminasesProtein-Arginine Deiminase Type 4antigen presentationcheckpointcitrullinationCP: CancerCP: ImmunologyimmunotherapymacrophageMHCPAD4PIASSTAT1T celltumor

Identifiers

PMID38489266
PMCPMC11022165
OpenAlexW4392769596

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

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.