Evidence map›Paper›PMID 24162015›Full record

ArticleOncotarget2013

Alterations of immune response of Non-Small Cell Lung Cancer with Azacytidine.

John Wrangle, Wei Wang, Alexander Koch, Hariharan Easwaran, Helai P Mohammad, Frank Vendetti, Wim Vancriekinge, Timothy Demeyer, Zhengzong Du, Princy Parsana and 18 more

Registry-linked trialOpen access · hybridAbstract read
In one paragraph

Article in Oncotarget, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03941496 (Phase 1b/2a Safety and Immunogenicity of the DNMT Inhibitor Azacitidine During Anti-Tuberculosis Therapy), which is not on this map. Cited by 242 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
242citing papers in PubMed, 1 pooled it
13.4field-weighted citation impact, top 1% 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.

NCT03941496 phase1 / phase2withdrawnnot on this mapstarted 2022, after this paper: background citation

Phase 1b/2a Safety and Immunogenicity of the DNMT Inhibitor Azacitidine During Anti-Tuberculosis Therapy

TypeinterventionalSponsorAndrew DinardoRan2022 to 2023Enrolled0ConditionsTuberculosis, PulmonaryArmsAzacitidine Injection
3 · Its place in the literature

Who cites it

242 citing papers in PubMed, 1 synthesis or guideline pooled it, 386 citations in OpenAlex.

  1. Pooled it
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  8. Phase I Study of CC-486 Alone and in Combination with Carboplatin or nab-Paclitaxel in Patients with Relapsed or Refractory Solid Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018
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  17. Epigenetic mechanisms of HIV and opioid-induced neuropathology: Potential therapies and interventions.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  18. Review
  19. Article
  20. Review

182 more citing papers are in PubMed but not listed here.

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

28 authors at 8 institutions in 2 countries.

John WrangleThe Johns Hopkins University, School of Medicine, Oncology Center-Hematology/Medical Oncology, Baltimore, Maryland.
Wei Wang
Alexander Koch
Hariharan Easwaran
Helai P Mohammad
Frank Vendetti
Wim Vancriekinge
Timothy Demeyer
Zhengzong Du
Princy Parsana
Kristen Rodgers
Ray-Whay Yen
Cynthia A Zahnow
Janis M Taube
Julie R Brahmer
Scott S Tykodi
Keith Easton
Richard D Carvajal
Peter A Jones
Peter W Laird
Daniel J Weisenberger
Salina Tsai
Rosalyn A Juergens
Suzanne L Topalian
Charles M Rudin
Malcolm V Brock
Drew Pardoll
Stephen B Baylin
Johns Hopkins University · USJohns Hopkins Medicine · USGhent University · BEUniversity of Southern California · USFred Hutch Cancer Center · USGlaxoSmithKline (United States) · USMemorial Sloan Kettering Cancer Center · USSeattle Cancer Care Alliance · US

Funding

TARGETING EARLY CHANGES FOR NEW SCREENING STRATEGIESP50CA058184 · NCI · JOHNS HOPKINS UNIVERSITY · PI BISWAL, SHYAM · 1992 to 2013
$30.5M
MECHANISMS OF DE NOVO METHYLATION IN CANCERR01CA082422 · NCI · VAN ANDEL RESEARCH INSTITUTE · PI JONES, PETER A · 1999 to 2016
$5.1M
NCI NIH HHS CA058184NCI NIH HHS P50 CA058184NCI NIH HHS R01 CA082422
6 · The paper itself

Abstract

Innovative therapies are needed for advanced Non-Small Cell Lung Cancer (NSCLC). We have undertaken a genomics based, hypothesis driving, approach to query an emerging potential that epigenetic therapy may sensitize to immune checkpoint therapy targeting PD-L1/PD-1 interaction. NSCLC cell lines were treated with the DNA hypomethylating agent azacytidine (AZA - Vidaza) and genes and pathways altered were mapped by genome-wide expression and DNA methylation analyses. AZA-induced pathways were analyzed in The Cancer Genome Atlas (TCGA) project by mapping the derived gene signatures in hundreds of lung adeno (LUAD) and squamous cell carcinoma (LUSC) samples. AZA up-regulates genes and pathways related to both innate and adaptive immunity and genes related to immune evasion in a several NSCLC lines. DNA hypermethylation and low expression of IRF7, an interferon transcription factor, tracks with this signature particularly in LUSC. In concert with these events, AZA up-regulates PD-L1 transcripts and protein, a key ligand-mediator of immune tolerance. Analysis of TCGA samples demonstrates that a significant proportion of primary NSCLC have low expression of AZA-induced immune genes, including PD-L1. We hypothesize that epigenetic therapy combined with blockade of immune checkpoints - in particular the PD-1/PD-L1 pathway - may augment response of NSCLC by shifting the balance between immune activation and immune inhibition, particularly in a subset of NSCLC with low expression of these pathways. Our studies define a biomarker strategy for response in a recently initiated trial to examine the potential of epigenetic therapy to sensitize patients with NSCLC to PD-1 immune checkpoint blockade.

Indexed as

Antimetabolites, AntineoplasticAzacitidineB7-H1 AntigenCarcinoma, Non-Small-Cell LungCell Line, TumorDNA MethylationEpigenomicsHumansImmunotherapyLung NeoplasmsProgrammed Cell Death 1 ReceptorSignal TransductionUp-RegulationAntimetabolites, AntineoplasticAzacitidineB7-H1 AntigenCD274 protein, humanPDCD1 protein, humanProgrammed Cell Death 1 Receptor

Identifiers

PMID24162015
PMCPMC3875770
OpenAlexW1827923022

What OpenQuestion holds

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Read underepoch 390

Registered trials

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.