Evidence map›Paper›PMID 37468584›Full record

ReviewNature2023

The complementarity of DDR, nucleic acids and anti-tumour immunity.

Anand V R Kornepati, Cody M Rogers, Patrick Sung, Tyler J Curiel

2 registry-linked trialsAbstract readReview
PubMed Publisher
In one paragraph

Review in Nature, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 64 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed, 2 pooled it
27.6field-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.

NCT06168487 phase1recruitingnot on this mapstarted 2024, after this paper: background citation

Phase I Non-Randomized, Unblinded, Single-Center Trial of Oral Telmisartan Alone or Combined With Selected Standard of Care Therapies for Prostate Cancer

TypeinterventionalSponsorTyler J CurielRan2024 to 2027Enrolled36ConditionsProstate CancerArmsTelmisartan, Standard of Care Regimen
NCT06815497 phase2recruitingnot on this mapstarted 2026, after this paper: background citation

Phase II Non-Randomized, Unblinded, Single-Center Trial of Telmisartan in Combination With Cytotoxic Regimens in Platinum-Resistant Ovarian Cancer Versus Historical Best Supportive Care

TypeinterventionalSponsorTyler J CurielRan2026 to 2029Enrolled33ConditionsOvarian CancerArmsTelmisartan
3 · Its place in the literature

Who cites it

64 citing papers in PubMed, 2 syntheses or guidelines pooled it, 118 citations in OpenAlex.

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  5. DONSON links tumor-cell survival to MIF-associated macrophage remodeling in small cell lung cancer.Apoptosis : an international journal on programmed cell death · 2026
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4 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

4 authors at 3 institutions in 2 countries.

Anand V R KornepatiGraduate School of Biomedical Sciences, University of Texas Health, San Antonio, TX, USA.
Cody M RogersDepartment of Biochemistry and Structural Biology, University of Texas Health, San Antonio, TX, USA.
Patrick SungGraduate School of Biomedical Sciences, University of Texas Health, San Antonio, TX, USA.ORCID 0000-0003-1396-9040
Tyler J CurielGraduate School of Biomedical Sciences, University of Texas Health, San Antonio, TX, USA. tyler.j.curiel@dartmouth.edu.ORCID 0000-0001-6962-9411
The University of Texas Health Science Center at San Antonio · USDartmouth College · USThe University of Texas MD Anderson Cancer Center · US

Funding

Bladder cancer PD-L1 control of homologous recombination: Basic mechanisms applied to novel treatmentsR01CA268641 · NCI · DARTMOUTH-HITCHCOCK CLINIC · PI Tyler J. Curiel, WEIXING Wilson ZHAO · 2022 to 2026
$2.5M
Role of cell-intrinsic effects of PD-L1 in carcinogenesisF30CA239390 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI KORNEPATI, ANAND · 2020 to 2023
$130k
NCI NIH HHS F30 CA239390NCI NIH HHS R01 CA054150NCI NIH HHS R01 CA268641NCI NIH HHS R35 CA024180
6 · The paper itself

Abstract

Immune checkpoint blockade (ICB) immunotherapy is a first-line treatment for selected cancers, yet the mechanisms of its efficacy remain incompletely understood. Furthermore, only a minority of patients with cancer benefit from ICB, and there is a lack of fully informative treatment response biomarkers. Selectively exploiting defects in DNA damage repair is also a standard treatment for cancer, spurred by enhanced understanding of the DNA damage response (DDR). DDR and ICB are closely linked-faulty DDR produces immunogenic cancer neoantigens that can increase the efficacy of ICB therapy, and tumour mutational burden is a good but imperfect biomarker for the response to ICB. DDR studies in ICB efficacy initially focused on contributions to neoantigen burden. However, a growing body of evidence suggests that ICB efficacy is complicated by the immunogenic effects of nucleic acids generated from exogenous DNA damage or endogenous processes such as DNA replication. Chemotherapy, radiation, or selective DDR inhibitors (such as PARP inhibitors) can generate aberrant nucleic acids to induce tumour immunogenicity independently of neoantigens. Independent of their functions in immunity, targets of immunotherapy such as cyclic GMP-AMP synthase (cGAS) or PD-L1 can crosstalk with DDR or the DNA repair machinery to influence the response to DNA-damaging agents. Here we review the rapidly evolving, multifaceted interfaces between DDR, nucleic acid immunogenicity and immunotherapy efficacy, focusing on ICB. Understanding these interrelated processes could explain ICB treatment failures and reveal novel exploitable therapeutic vulnerabilities in cancers. We conclude by addressing major unanswered questions and new research directions.

Indexed as

DNA DamageImmune Checkpoint InhibitorsImmunotherapyNeoplasmsNucleic AcidsAntigens, NeoplasmB7-H1 AntigenBiomarkers, TumorCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseDNA RepairDNA ReplicationHumansMutationPoly(ADP-ribose) Polymerase InhibitorsAntigens, NeoplasmB7-H1 AntigenBiomarkers, TumorCD274 protein, humancGAS protein, humanCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseImmune Checkpoint InhibitorsNucleic AcidsPoly(ADP-ribose) Polymerase Inhibitors

Identifiers

PMID37468584
OpenAlexW4384819845

What OpenQuestion holds

Textmetadata
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.