Evidence map›Paper›PMID 36757811›Full record

ArticleThe Journal of clinical investigation2023

PP2Ac/STRN4 negatively regulates STING-type I IFN signaling in tumor-associated macrophages.

Winson S Ho, Isha Mondal, Beisi Xu, Oishika Das, Raymond Sun, Pochin Chiou, Xiaomin Cai, Foozhan Tahmasebinia, Elizabeth McFadden, Caren Yu-Ju Wu and 5 more

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

Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
5.8field-weighted citation impact, top 4% 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

32 citing papers in PubMed, 35 citations in OpenAlex.

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  19. Protein Phosphatase 2A Promotes CD8Research (Washington, D.C.) · 2025
    Article
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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

15 authors at 6 institutions in 1 country.

Winson S HoDepartment of Neurosurgery, Dell Medical School, The University of Texas at Austin, Austin, Texas, USA.
Isha MondalDepartment of Neurosurgery, Dell Medical School, The University of Texas at Austin, Austin, Texas, USA.
Beisi XuCenter for Applied Bioinformatics, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Oishika DasDepartment of Neurosurgery, Dell Medical School, The University of Texas at Austin, Austin, Texas, USA.
Raymond SunDepartment of Neurosurgery, Dell Medical School, The University of Texas at Austin, Austin, Texas, USA.
Pochin ChiouDepartment of Neurosurgery, Dell Medical School, The University of Texas at Austin, Austin, Texas, USA.
Xiaomin CaiDepartment of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, Florida, USA.
Foozhan TahmasebiniaDepartment of Biological Sciences, Southern Methodist University, Dallas, Texas, USA.
Elizabeth McFaddenDepartment of Molecular Sciences, University of Texas at Austin, Austin, Texas, USA.
Caren Yu-Ju WuDepartment of Neurosurgery, Stanford University, Stanford, California, USA.
Zhihao WuDepartment of Biological Sciences, Southern Methodist University, Dallas, Texas, USA.
William MatsuiDepartment of Oncology, Dell Medical School, The University of Texas at Austin, Austin, Texas, USA.
Michael LimDepartment of Neurosurgery, Stanford University, Stanford, California, USA.
Zhipeng MengDepartment of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, Florida, USA.
Rongze Olivia LuDepartment of Neurosurgery, Dell Medical School, The University of Texas at Austin, Austin, Texas, USA.
The University of Texas at Austin · USSouthern Methodist University · USStanford University · USUniversity of Miami · USSt. Jude Children's Research Hospital · USUCSF Helen Diller Family Comprehensive Cancer Center · US

Funding

Transitioning Early Career Neurosurgeons to Scientific IndependenceK12NS080223 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI ESKANDAR, EMAD N · 2012 to 2022
$9.2M
Roles of mechanotransduction in organ regeneration and fibrosisR35GM142504 · NIGMS · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI MENG, ZHIPENG · 2021 to 2025
$2.0M
Regulation of Macrophage- and Microglia-mediated STING Signaling in GlioblastomaR01NS126501 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Rongze Olivia Lu · 2022 to 2026
$1.9M
NIGMS NIH HHS R35 GM142504NINDS NIH HHS K12 NS080223NINDS NIH HHS R01 NS126501
6 · The paper itself

Abstract

Stimulator of IFN genes type I (STING-Type I) IFN signaling in myeloid cells plays a critical role in effective antitumor immune responses, but STING agonists as monotherapy have shown limited efficacy in clinical trials. The mechanisms that downregulate STING signaling are not fully understood. Here, we report that protein phosphatase 2A (PP2A), with its specific B regulatory subunit Striatin 4 (STRN4), negatively regulated STING-Type I IFN in macrophages. Mice with macrophage PP2A deficiency exhibited reduced tumor progression. The tumor microenvironment showed decreased immunosuppressive and increased IFN-activated macrophages and CD8+ T cells. Mechanistically, we demonstrated that Hippo kinase MST1/2 was required for STING activation. STING agonists induced dissociation of PP2A from MST1/2 in normal macrophages, but not in tumor conditioned macrophages. Furthermore, our data showed that STRN4 mediated PP2A binding to and dephosphorylation of Hippo kinase MST1/2, resulting in stabilization of YAP/TAZ to antagonize STING activation. In human patients with glioblastoma (GBM), YAP/TAZ was highly expressed in tumor-associated macrophages but not in nontumor macrophages. We also demonstrated that PP2A/STRN4 deficiency in macrophages reduced YAP/TAZ expression and sensitized tumor-conditioned macrophages to STING stimulation. In summary, we demonstrated that PP2A/STRN4-YAP/TAZ has, in our opinion, been an unappreciated mechanism that mediates immunosuppression in tumor-associated macrophages, and targeting the PP2A/STRN4-YAP/TAZ axis can sensitize tumors to immunotherapy.

Indexed as

GlioblastomaTumor-Associated MacrophagesAnimalsCalmodulin-Binding ProteinsHumansInterferon Type IMacrophagesMiceProtein Processing, Post-TranslationalSignal TransductionTumor MicroenvironmentCalmodulin-Binding ProteinsInterferon Type ISTRN4 protein, humanCancer immunotherapyImmunologyMacrophagesOncology

Identifiers

PMID36757811
PMCPMC10014107
OpenAlexW4319657048

What OpenQuestion holds

Textfull text, public
LicenceCC BY
measurements read58
identifiers read1
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.