Evidence map›Paper›PMID 31653912›Full record

ArticleNature communications2019

Antitumor immunity augments the therapeutic effects of p53 activation on acute myeloid leukemia.

Yasutaka Hayashi, Susumu Goyama, XiaoXiao Liu, Moe Tamura, Shuhei Asada, Yosuke Tanaka, Tomofusa Fukuyama, Mark Wunderlich, Eric O'Brien, Benjamin Mizukawa and 8 more

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

Article in Nature communications, 2019. 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
4.9field-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, 53 citations in OpenAlex.

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  12. ANPELA: Significantly Enhanced Quantification Tool for Cytometry-Based Single-Cell Proteomics.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023
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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

18 authors at 4 institutions in 2 countries.

Yasutaka HayashiDivision of Cellular Therapy, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Susumu GoyamaDivision of Cellular Therapy, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. goyama@ims.u-tokyo.ac.jp.
XiaoXiao LiuDivision of Cellular Therapy, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.ORCID http://orcid.org/0000-0002-0023-4013
Moe TamuraDivision of Cellular Therapy, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Shuhei AsadaDivision of Cellular Therapy, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.ORCID http://orcid.org/0000-0001-6116-7996
Yosuke TanakaDivision of Cellular Therapy, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Tomofusa FukuyamaDivision of Cellular Therapy, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.ORCID http://orcid.org/0000-0002-0709-3188
Mark WunderlichCancer & Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Eric O'BrienCancer & Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Benjamin MizukawaCancer & Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Satoshi YamazakiDivision of Stem Cell Therapy, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Akiko MatsumotoLaboratory of Molecular Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Satoshi YamasakiLaboratory of Molecular Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Tatsuhiro ShibataLaboratory of Molecular Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Koichi MatsudaLaboratory of Clinical Genome Sequencing, Department of Computational biology and medical Sciences, Graduate school of Frontier Sciences, The University of Tokyo, Tokyo, Japan.ORCID http://orcid.org/0000-0001-7292-2686
Goro SashidaLaboratory of Transcriptional Regulation in Leukemogenesis, International Research Center for Medical Sciences, Kumamoto University, Kumamoto, Japan.ORCID http://orcid.org/0000-0003-2318-5987
Hitoshi TakizawaLaboratory of Stem Cell Stress, International Research Center for Medical Sciences, Kumamoto University, Kumamoto, Japan.
Toshio KitamuraDivision of Cellular Therapy, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. kitamura@ims.u-tokyo.ac.jp.
The University of Tokyo · JPCincinnati Children's Hospital Medical Center · USKumamoto University · JPTokyo Medical University · JP

Funding

Therapeutic insights through patient derived leukemia xenograftsR50CA211404 · NCI · CINCINNATI CHILDRENS HOSP MED CTR · PI Mark Wunderlich · 2016 to 2026
$1.9M
NCI NIH HHS R50 CA211404
6 · The paper itself

Abstract

The negative regulator of p53, MDM2, is frequently overexpressed in acute myeloid leukemia (AML) that retains wild-type TP53 alleles. Targeting of p53-MDM2 interaction to reactivate p53 function is therefore an attractive therapeutic approach for AML. Here we show that an orally active inhibitor of p53-MDM2 interaction, DS-5272, causes dramatic tumor regressions of MLL-AF9-driven AML in vivo with a tolerable toxicity. However, the antileukemia effect of DS-5272 is markedly attenuated in immunodeficient mice, indicating the critical impact of systemic immune responses that drive p53-mediated leukemia suppression. In relation to this, DS-5272 triggers immune-inflammatory responses in MLL-AF9 cells including upregulation of Hif1α and PD-L1, and inhibition of the Hif1α-PD-L1 axis sensitizes AML cells to p53 activation. We also found that NK cells are important mediators of antileukemia immunity. Our study showed the potent activity of a p53-activating drug against AML, which is further augmented by antitumor immunity.

Indexed as

AnimalsB7-H1 AntigenHumansHypoxia-Inducible Factor 1, alpha SubunitImidazolesImmunotherapyInflammationKiller Cells, NaturalLeukemia, Myeloid, AcuteMiceMice, Inbred NODMice, KnockoutMice, SCIDNeoplasm TransplantationProto-Oncogene Proteins c-mdm2ThiazolesB7-H1 AntigenCd274 protein, mouseDS-5272Hif1a protein, mouseHypoxia-Inducible Factor 1, alpha SubunitImidazolesMdm2 protein, mouseProto-Oncogene Proteins c-mdm2ThiazolesTrp53 protein, mouseTumor Suppressor Protein p53

Identifiers

PMID31653912
PMCPMC6814808
OpenAlexW2981374542

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.