Evidence map›Paper›PMID 39313308›Full record

ArticleJournal for immunotherapy of cancer2024

MTA-cooperative PRMT5 inhibitors enhance T cell-mediated antitumor activity in MTAP-loss tumors.

Si Chen, Jiakai Hou, Roshni Jaffery, Ashley Guerrero, Rongjie Fu, Leilei Shi, Ningbo Zheng, Ritu Bohat, Nicholas A Egan, Chengtai Yu and 13 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal for immunotherapy of cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing 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

15 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Comprehensive Genomic and Transcriptomic Characterization of MTAP Loss across Advanced Solid Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
    Observational
  5. Article
  6. Review
  7. Article
  8. Review
  9. Review
  10. Article
  11. Review
  12. Interferon Epsilon Loss Is Elusive 9p21 Link to Immune-Cold Tumors, Resistant to Immune Checkpoint Therapy, and Endogenous CXCL9/10 Induction.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2025
    Review
  13. Review
  14. Article
  15. 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

23 authors.

Si ChenBiology and Biochemistry, University of Houston, Houston, Texas, USA.
Jiakai HouBiology and Biochemistry, University of Houston, Houston, Texas, USA.
Roshni JafferyBiology and Biochemistry, University of Houston, Houston, Texas, USA.
Ashley GuerreroBiology and Biochemistry, University of Houston, Houston, Texas, USA.
Rongjie FuEpigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Leilei ShiEpigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Ningbo ZhengBiology and Biochemistry, University of Houston, Houston, Texas, USA.
Ritu BohatBiology and Biochemistry, University of Houston, Houston, Texas, USA.
Nicholas A EganBiology and Biochemistry, University of Houston, Houston, Texas, USA.
Chengtai YuBiology and Biochemistry, University of Houston, Houston, Texas, USA.
Sana SharifPharmacological and Pharmaceutical Sciences, University of Houston, Houston, Texas, USA.
Yue LuEpigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Wei HeEpigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Shuyue WangEpigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Donjeta GjukaMolecular Biosciences, The University of Texas at Austin, Austin, Texas, USA.
Everett M StoneMolecular Biosciences, The University of Texas at Austin, Austin, Texas, USA.
Pooja Anil ShahInvestigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Jordi Rodon AhnertInvestigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Taiping ChenEpigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Xinli LiuPharmacological and Pharmaceutical Sciences, University of Houston, Houston, Texas, USA.
Mark T BedfordEpigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Han XuEpigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Weiyi PengBiology and Biochemistry, University of Houston, Houston, Texas, USA wpeng2@central.uh.edu.ORCID http://orcid.org/0000-0002-7785-6240

Funding

Computational approaches for protein functional analysis using CRISPR screensR35GM137927 · NIGMS · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI XU, HAN · 2020 to 2024
$2.0M
Development and Mechanistic Studies of an Engineered Human Enzyme to Abrogate Immune Suppression due to Elevated Methylthioadenosine (MTA) by MTAP null/low TumorsR01CA240700 · NCI · UNIVERSITY OF TEXAS AT AUSTIN · PI STONE, EVERETT · 2019 to 2023
$1.9M
NCI NIH HHS R01 CA240700NIGMS NIH HHS R35 GM137927
6 · The paper itself

Abstract

backgroundHyperactivated protein arginine methyltransferases (PRMTs) are implicated in human cancers. Inhibiting tumor intrinsic PRMT5 was reported to potentiate antitumor immune responses, highlighting the possibility of combining PRMT5 inhibitors (PRMT5i) with cancer immunotherapy. However, global suppression of PRMT5 activity impairs the effector functions of immune cells. Here, we sought to identify strategies to specifically inhibit PRMT5 activity in tumor tissues and develop effective PRMT5i-based immuno-oncology (IO) combinations for cancer treatment, particularly for methylthioadenosine phosphorylase (MTAP)-loss cancer.

methodsIsogeneic tumor lines with and without MTAP loss were generated by CRISPR/Cas9 knockout. The effects of two PRMT5 inhibitors (GSK3326595 and MRTX1719) were evaluated in these isogenic tumor lines and T cells

resultsGSK3326595 significantly suppresses PRMT5 activity in tumors and T cells regardless of the MTAP status. However, MRTX1719, a methylthioadenosine-cooperative PRMT5 inhibitor, exhibits tumor-specific PRMT5 inhibition in MTAP-loss tumors with limited immunosuppressive effects. Mechanistically, transcriptomic and proteomic profiling analysis reveals that MRTX1719 successfully reduces the activation of the PI3K pathway, a well-documented immune-resistant pathway. It highlights the potential of MRTX1719 to overcome immune resistance in MTAP-loss tumors. In addition, MRTX1719 sensitizes MTAP-loss tumor cells to the killing of tumor-reactive T cells. Combining MRTX1719 and anti-PD-1 leads to superior antitumor activity in mice bearing MTAP-loss tumors.

conclusionCollectively, our results provide a strong rationale and mechanistic insights for the clinical development of MRTX1719-based IO combinations in MTAP-loss tumors.

Indexed as

Protein-Arginine N-MethyltransferasesPurine-Nucleoside PhosphorylaseAnimalsCell Line, TumorFemaleHumansIsoquinolinesMiceNeoplasmsPyrimidinesT-Lymphocytes5'-methylthioadenosine phosphorylaseGSK3235025IsoquinolinesPRMT5 protein, humanPrmt5 protein, mouseProtein-Arginine N-MethyltransferasesPurine-Nucleoside PhosphorylasePyrimidinesCombination therapyImmunotherapy

Identifiers

PMID39313308
PMCPMC11418539

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.