Evidence map›Paper›PMID 39851178›Full record

ArticleCancer research communications2025

PARP Inhibitors Differentially Regulate Immune Responses in Distinct Genetic Backgrounds of High-Grade Serous Tubo-Ovarian Carcinoma.

Luiza Doro Pereira, Monica Wielgos-Bonvallet, Selim Misirlioglu, Alireza Khodadai-Jamayran, Petar Jelinic, Douglas A Levine

Erratum issuedAbstract read
In one paragraph

Article in Cancer research communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

Luiza Doro Pereira *Division of Gynecologic Oncology, Department of OB/GYN, Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, New York, New York.ORCID 0009-0007-6858-5868
Monica Wielgos-Bonvallet *Division of Gynecologic Oncology, Department of OB/GYN, Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, New York, New York.ORCID 0009-0007-0009-2629
Selim MisirliogluDivision of Gynecologic Oncology, Department of OB/GYN, Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, New York, New York.ORCID 0000-0002-5390-6637
Alireza Khodadai-JamayranDepartment of Pathology, Applied Bioinformatics Laboratories, NYU School of Medicine, New York, New York.ORCID 0000-0003-2495-7504
Petar JelinicDivision of Gynecologic Oncology, Department of OB/GYN, Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, New York, New York.ORCID 0009-0008-8554-6286
Douglas A LevineDivision of Gynecologic Oncology, Department of OB/GYN, Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, New York, New York.ORCID 0000-0003-1038-8232

Funding

Project-005UL1TR001445 · NCATS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI BREDELLA, MIRIAM ANTOINETTE, HOCHMAN, JUDITH S · 2015 to 2025
$103.5M
NRSA Training CoreTL1TR001447 · NCATS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI MICOLI, KEITH J. · 2015 to 2025
$5.9M
NCATS NIH HHS TL1 TR001447NCATS NIH HHS UL1 TR001445
6 · The paper itself

Abstract

abstractImmune checkpoint inhibitors (ICI) have revolutionized treatment for several tumor indications without demonstrated benefit for patients with ovarian cancer. To improve the therapeutic ratio of ICIs in patients with ovarian cancer, several different clinical trials are testing combinations with poly(ADP-ribose) polymerase (PARP) inhibitors. Comparing the immunomodulatory effects of clinically advanced PARP inhibitors (PARPi) may help to identify the best partner to combine with ICIs. We examined the treatment effect of talazoparib (a PARP trapper) and veliparib (a solely PARP enzymatic inhibitor) in homologous recombination deficient (HRD) and homologous recombination proficient high-grade serous tubo-ovarian carcinoma (HGSC) cell lines on immune-related gene expression. We discovered and validated that CXCL8, IL-6, and TNF gene expression were upregulated after talazoparib treatment in both OVCAR3 (HRD) and CAOV3 homologous recombination proficient HGSC cell lines. In contrast, veliparib treatment slightly elevated similar genes exclusively in an HRD HGSC cell line model. We expanded these studies to include olaparib, a PARP trapper less potent than talazoparib, and found effects specific to COV361 (BRCA1 mutant) and OVCAR8 (BRCA1 methylated) HGSC cells but not all HRD HGSC cell lines. Our studies also identified differences among PARP trappers versus veliparib on augmenting CXCL10 expression. Finally, we show that talazoparib modulates the CXCL10 response in cGAS-defective cell lines, independent of the cGAS-STING pathway. These mechanistic studies advance our understanding of how different PARPis affect the immune system in various genetic backgrounds. SIGNIFICANCE: This work highlights how different PARPis, especially talazoparib, modulate immune-related gene expression in ovarian cancer cells, independent of the cGAS-STING pathway. These findings may improve our understanding of how different PARPis affect the immune system in various genetic backgrounds.

Indexed as

Cystadenocarcinoma, SerousOvarian NeoplasmsPoly(ADP-ribose) Polymerase InhibitorsCell Line, TumorFemaleGene Expression Regulation, NeoplasticHumansMembrane ProteinsNucleotidyltransferasesPhthalazinesSignal TransductionSTING ProteinMembrane ProteinsNucleotidyltransferasesPhthalazinesPoly(ADP-ribose) Polymerase InhibitorsSTING1 protein, humanSTING Protein

Identifiers

PMID39851178
PMCPMC11836641

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Registered trials

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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.