Evidence map›Paper›PMID 30828801›Full record

ArticleBritish journal of haematology2019

Hypomethylating agent alters the immune microenvironment in acute myeloid leukaemia (AML) and enhances the immunogenicity of a dendritic cell/AML vaccine.

Myrna R Nahas, Dina Stroopinsky, Jacalyn Rosenblatt, Leandra Cole, Athalia R Pyzer, Eleni Anastasiadou, Anna Sergeeva, Adam Ephraim, Abigail Washington, Shira Orr and 11 more

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

Article in British journal of haematology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
3.2field-weighted citation impact, top 7% 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

51 citing papers in PubMed, 72 citations in OpenAlex.

  1. Trial
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  5. Molecularly targeted therapy and immunotherapy in leukemias.Journal of hematology & oncology · 2026
    Review
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  7. Article
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  15. Targeting one-carbon metabolism for cancer immunotherapy.Clinical and translational medicine · 2024
    Review
  16. Review
  17. Identification of tumor antigens and immune subtypes of acute myeloid leukemia for mRNA vaccine development.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023
    Article
  18. Article
  19. Review
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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

21 authors at 3 institutions in 1 country.

Myrna R NahasBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-6864-0931
Dina StroopinskyBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-9749-2704
Jacalyn RosenblattBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Leandra ColeBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Athalia R PyzerBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Eleni AnastasiadouBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Anna SergeevaThe University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Adam EphraimBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Abigail WashingtonBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Shira OrrBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Malgorzata McMastersBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Matthew WeinstockBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Salvia JainBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Rebecca K LeafBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Haider GhiasuddinBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Maryam RahimianBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Jessica LiegelBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Jeffrey J MolldremThe University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Frank SlackBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Donald KufeDana-Farber Cancer Institute, Department of Medical Oncology, Boston, MA.
David AviganBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Beth Israel Deaconess Medical Center · USThe University of Texas MD Anderson Cancer Center · USDana-Farber Cancer Institute · US

Funding

Targeting SYK Kinase in AMLP50CA206963 · NCI · DANA-FARBER CANCER INST · PI ASTER, JON C. · 2017 to 2021
$10.6M
NCI NIH HHS P50 CA206963
6 · The paper itself

Abstract

Acute myeloid leukaemia (AML) is a lethal haematological malignancy characterized by an immunosuppressive milieu in the tumour microenvironment (TME) that fosters disease growth and therapeutic resistance. Hypomethylating agents (HMAs) demonstrate clinical efficacy in AML patients and exert immunomodulatory activities. In the present study, we show that guadecitabine augments both antigen processing and presentation, resulting in increased AML susceptibility to T cell-mediated killing. Exposure to HMA results in the activation of the endogenous retroviral pathway with concomitant downstream amplification of critical mediators of inflammation. In an immunocompetent murine leukaemia model, guadecitabine negatively regulates inhibitory accessory cells in the TME by decreasing PD-1 (also termed PDCD1) expressing T cells and reducing AML-mediated expansion of myeloid-derived suppressor cells. Therapy with guadecitabine results in enhanced leukaemia-specific immunity, as manifested by increased CD4 and CD8 cells targeting syngeneic leukaemia cells. We have previously reported that vaccination with AML/dendritic cell fusions elicits the expansion of leukaemia-specific T cells and protects against disease relapse. In the present study, we demonstrate that vaccination in conjunction with HMA therapy results in enhanced anti-leukaemia immunity and survival. The combination of a novel personalized dendritic cell/AML fusion vaccine and an HMA has therapeutic potential, and a clinical trial investigating this combination is planned.

Indexed as

AnimalsAntineoplastic Agents, ImmunologicalAzacitidineCancer VaccinesCD8-Positive T-LymphocytesCell Line, TumorDendritic CellsDisease Models, AnimalDNA MethylationDown-RegulationHumansImmunity, CellularLeukemia, Myeloid, AcuteMice, Inbred C57BLNeoplasm TransplantationProgrammed Cell Death 1 ReceptorAntineoplastic Agents, ImmunologicalAzacitidineCancer VaccinesguadecitabinePdcd1 protein, mouseProgrammed Cell Death 1 Receptoracute myeloid leukaemiadendritic cell vaccineendogenous retroviral pathwayhypomethylating agentimmunotherapy

Identifiers

PMID30828801
PMCPMC6590084
OpenAlexW2918453079

What OpenQuestion holds

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LicenceTDM
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.