Evidence map›Paper›PMID 34970273›Full record

ReviewFrontiers in immunology2021

Function and Molecular Mechanism of the DNA Damage Response in Immunity and Cancer Immunotherapy.

Zu Ye, Yin Shi, Susan P Lees-Miller, John A Tainer

Open access · goldAbstract readReview
In one paragraph

Review in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed, 1 pooled it
4.3field-weighted citation impact, top 5% 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

57 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.

  1. Pooled it
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  15. Elucidating DNA Damage-Dependent Immune System Activation.International journal of molecular sciences · 2025
    Review
  16. Review
  17. Article
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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

4 authors at 3 institutions in 3 countries.

Zu YeDepartment of Molecular and Cellular Oncology, and Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Yin ShiDepartment of Immunology, Zhejiang University School of Medicine, Hangzhou, China.
Susan P Lees-MillerDepartment of Biochemistry and Molecular Biology, Robson DNA Science Centre, Charbonneau Cancer Institute, University of Calgary, Calgary, AB, Canada.
John A TainerDepartment of Molecular and Cellular Oncology, and Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
The University of Texas MD Anderson Cancer Center · USUniversity of Calgary · CAZhejiang University · CN

Funding

Transcription-Coupled & Replication-Associated Excision RepairP01CA092584 · NCI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI John A. Tainer · 2001 to 2026
$89.6M
Mesoscale and Nanoscale Technologies Integrated by Structures for DNA Repair Complexes (MANTIS-DRC)R35CA220430 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI John A. Tainer · 2018 to 2026
$7.6M
PHARMACOLOGICAL MODULATION OF POLY(ADP-RIBOSE) METABOLISMR01CA200231 · NCI · WASHINGTON UNIVERSITY · PI AHMED, ZAMAL, JONES, DARIN E. · 2016 to 2020
$1.7M
Orbitrap Elite High-Resolution Mass Spectrometer for Proteomics and MetabolomicsS10OD012304 · OD · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI HAWKE, DAVID H · 2013 to 2013
$877k
NCI NIH HHS P01 CA092584NCI NIH HHS R01 CA200231NCI NIH HHS R35 CA220430NIH HHS S10 OD012304
6 · The paper itself

Abstract

The DNA damage response (DDR) is an organized network of multiple interwoven components evolved to repair damaged DNA and maintain genome fidelity. Conceptually the DDR includes damage sensors, transducer kinases, and effectors to maintain genomic stability and accurate transmission of genetic information. We have recently gained a substantially improved molecular and mechanistic understanding of how DDR components are interconnected to inflammatory and immune responses to stress. DDR shapes both innate and adaptive immune pathways: (i) in the context of innate immunity, DDR components mainly enhance cytosolic DNA sensing and its downstream STimulator of INterferon Genes (STING)-dependent signaling; (ii) in the context of adaptive immunity, the DDR is needed for the assembly and diversification of antigen receptor genes that is requisite for T and B lymphocyte development. Imbalances between DNA damage and repair impair tissue homeostasis and lead to replication and transcription stress, mutation accumulation, and even cell death. These impacts from DDR defects can then drive tumorigenesis, secretion of inflammatory cytokines, and aberrant immune responses. Yet, DDR deficiency or inhibition can also directly enhance innate immune responses. Furthermore, DDR defects plus the higher mutation load in tumor cells synergistically produce primarily tumor-specific neoantigens, which are powerfully targeted in cancer immunotherapy by employing immune checkpoint inhibitors to amplify immune responses. Thus, elucidating DDR-immune response interplay may provide critical connections for harnessing immunomodulatory effects plus targeted inhibition to improve efficacy of radiation and chemotherapies, of immune checkpoint blockade, and of combined therapeutic strategies.

Indexed as

DNA DamageGenetic Predisposition to DiseaseImmunotherapyAdaptive ImmunityAnimalsBiomarkers, TumorDisease ManagementDisease SusceptibilityDNA-Activated Protein KinaseHumansImmunityImmunity, InnateImmunomodulationNeoplasmsV(D)J RecombinationBiomarkers, TumorDNA-Activated Protein Kinaseadaptive immunitycancer therapycGAS-STINGDNA damageDNA repairimmune responseimmunomodulatoryinnate immunity

Identifiers

PMID34970273
PMCPMC8712645
OpenAlexW4205380847

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.