Evidence map›Paper›PMID 29952768›Full record

ArticleThe Journal of clinical investigation2018

ATR kinase inhibitor AZD6738 potentiates CD8+ T cell-dependent antitumor activity following radiation.

Frank P Vendetti, Pooja Karukonda, David A Clump, Troy Teo, Ronald Lalonde, Katriana Nugent, Matthew Ballew, Brian F Kiesel, Jan H Beumer, Saumendra N Sarkar and 6 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 132 papers.

0numbers the graph read from it
0cells of the map it votes in
132citing papers in PubMed
9.0field-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.

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

132 citing papers in PubMed, 204 citations in OpenAlex.

  1. Article
  2. Article
  3. Targeted therapeutic strategies forTranslational lung cancer research · 2026
    Review
  4. Article
  5. ATR kinase inhibitors induce mitochondrial fission in CD8bioRxiv : the preprint server for biology · 2026
    Article
  6. Article
  7. Article
  8. Review
  9. Review
  10. Npj imaging · 2025
    Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Elucidating DNA Damage-Dependent Immune System Activation.International journal of molecular sciences · 2025
    Review
  16. Article
  17. Review
  18. Review
  19. Article
  20. Review

72 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

16 authors at 4 institutions in 4 countries.

Frank P VendettiDepartment of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Pooja KarukondaDepartment of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
David A ClumpDepartment of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Troy TeoDepartment of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Ronald LalondeDepartment of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Katriana NugentDepartments of Radiation Oncology and Molecular Radiation Sciences, Medical Oncology and Urology, Program in Cellular and Molecular Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
Matthew BallewDepartments of Radiation Oncology and Molecular Radiation Sciences, Medical Oncology and Urology, Program in Cellular and Molecular Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
Brian F KieselDepartment of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania, USA.
Jan H BeumerDepartment of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania, USA.
Saumendra N SarkarDepartment of Microbiology and Molecular Genetics and.
Thomas P ConradsInova Schar Cancer Institute, Inova Center for Personalized Health, Falls Church, Virginia, USA.
Mark J O'ConnorDNA Damage Response Biology Area, Oncology IMED, AstraZeneca, Cambridge, United Kingdom.
Robert L FerrisDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Phuoc T TranDepartments of Radiation Oncology and Molecular Radiation Sciences, Medical Oncology and Urology, Program in Cellular and Molecular Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
Greg M DelgoffeDepartment of Microbiology and Molecular Genetics and.
Christopher J BakkenistDepartment of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
University of Pittsburgh · USJohns Hopkins University · USAstraZeneca (United Kingdom) · GBInova Health System · US

Funding

VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Jessie Nedrow · 1988 to 2026
$158.0M
WILD TYPE P53-BASED ADJUVANT IMMUNOTHERAPY FOR SCCHNP50CA097190 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHRISTOPHER J. BAKKENIST · 2004 to 2026
$49.6M
NCI ET-CTN with Phase i Emphasis at UPCIUM1CA186690 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI JOHN C. BYRD, Farshid Dayyani · 2014 to 2026
$9.1M
Exploring and exploiting metabolic plasticity in regulatory T cellsDP2AI136598 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DELGOFFE, GREG M. · 2017 to 2017
$2.3M
Differential modulation of RIG-I and cGAS signaling by OASL and its role in antiviral response.R01AI118896 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SARKAR, SAUMENDRA N · 2015 to 2019
$2.1M
DNA damage signaling to immune checkpointsR01CA204173 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BAKKENIST, CHRISTOPHER J. · 2017 to 2021
$1.8M
Cancer Pharmacokinetics Research SpecialistR50CA211241 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI PARISE, ROBERT · 2016 to 2025
$1.8M
Structure-Functions Studies of Twist1-induced Radioresistance in Lung CancerR01CA166348 · NCI · JOHNS HOPKINS UNIVERSITY · PI TRAN, PHUOC T. · 2013 to 2017
$1.7M
NCI NIH HHS P30 CA047904NCI NIH HHS P50 CA097190NCI NIH HHS R01 CA166348NCI NIH HHS R01 CA204173NCI NIH HHS R50 CA211241NCI NIH HHS UM1 CA186690NIAID NIH HHS DP2 AI136598NIAID NIH HHS R01 AI118896
6 · The paper itself

Abstract

DNA-damaging chemotherapy and radiation therapy are integrated into the treatment paradigm of the majority of cancer patients. Recently, immunotherapy that targets the immunosuppressive interaction between programmed death 1 (PD-1) and its ligand PD-L1 has been approved for malignancies including non-small cell lung cancer, melanoma, and head and neck squamous cell carcinoma. ATR is a DNA damage-signaling kinase activated at damaged replication forks, and ATR kinase inhibitors potentiate the cytotoxicity of DNA-damaging chemotherapies. We show here that the ATR kinase inhibitor AZD6738 combines with conformal radiation therapy to attenuate radiation-induced CD8+ T cell exhaustion and potentiate CD8+ T cell activity in mouse models of Kras-mutant cancer. Mechanistically, AZD6738 blocks radiation-induced PD-L1 upregulation on tumor cells and dramatically decreases the number of tumor-infiltrating Tregs. Remarkably, AZD6738 combines with conformal radiation therapy to generate immunologic memory in complete responder mice. Our work raises the possibility that a single pharmacologic agent may enhance the cytotoxic effects of radiation while concurrently potentiating radiation-induced antitumor immune responses.

Indexed as

Adenocarcinoma of LungAnimalsAtaxia Telangiectasia Mutated ProteinsB7-H1 AntigenCD8-Positive T-LymphocytesCell Line, TumorChemoradiotherapyColorectal NeoplasmsHumansIndolesLymphocytes, Tumor-InfiltratingMiceMice, Inbred BALB CMorpholinesNeoplasms, ExperimentalProtein Kinase InhibitorsAtaxia Telangiectasia Mutated ProteinsAtr protein, mouseB7-H1 AntigenCd274 protein, mouseceralasertibHras protein, mouseIndolesMorpholinesProtein Kinase InhibitorsProto-Oncogene Proteins p21(ras)PyrimidinesSulfonamidesSulfoxidesCancerImmunologyOncology

Identifiers

PMID29952768
PMCPMC6118586
OpenAlexW2810414233

What OpenQuestion holds

Textmetadata
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.