STING agonism enhances anti-tumor immune responses and therapeutic efficacy of PARP inhibition in BRCA-associated breast cancer

Poly (ADP-ribose) polymerase (PARP) inhibitors exert their efficacy via synthetic lethal effects and by inducing cGAS/STING-mediated immune responses. We demonstrate that compared to monotherapies, combined PARP inhibition and STING agonism results in increased STING pathway activation, greater cyto...

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Autores principales: Pantelidou, Constantia, Jadhav, Heta, Kothari, Aditi, Liu, Renyan, Wulf, Gerburg M., Guerriero, Jennifer L., Shapiro, Geoffrey I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Brief Communication
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9448789/
https://www.ncbi.nlm.nih.gov/pubmed/36068244
http://dx.doi.org/10.1038/s41523-022-00471-5
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author Pantelidou, Constantia
Jadhav, Heta
Kothari, Aditi
Liu, Renyan
Wulf, Gerburg M.
Guerriero, Jennifer L.
Shapiro, Geoffrey I.
author_facet Pantelidou, Constantia
Jadhav, Heta
Kothari, Aditi
Liu, Renyan
Wulf, Gerburg M.
Guerriero, Jennifer L.
Shapiro, Geoffrey I.
author_sort Pantelidou, Constantia
collection PubMed
description Poly (ADP-ribose) polymerase (PARP) inhibitors exert their efficacy via synthetic lethal effects and by inducing cGAS/STING-mediated immune responses. We demonstrate that compared to monotherapies, combined PARP inhibition and STING agonism results in increased STING pathway activation, greater cytotoxic T-cell recruitment and enhanced dendritic cell activation in BRCA1-deficient breast cancer models. The combination markedly improved anti-tumor efficacy in vivo, with evidence of complete tumor clearance, prolongation of survival and induction of immunologic memory.
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spelling pubmed-94487892022-09-08 STING agonism enhances anti-tumor immune responses and therapeutic efficacy of PARP inhibition in BRCA-associated breast cancer Pantelidou, Constantia Jadhav, Heta Kothari, Aditi Liu, Renyan Wulf, Gerburg M. Guerriero, Jennifer L. Shapiro, Geoffrey I. NPJ Breast Cancer Brief Communication Poly (ADP-ribose) polymerase (PARP) inhibitors exert their efficacy via synthetic lethal effects and by inducing cGAS/STING-mediated immune responses. We demonstrate that compared to monotherapies, combined PARP inhibition and STING agonism results in increased STING pathway activation, greater cytotoxic T-cell recruitment and enhanced dendritic cell activation in BRCA1-deficient breast cancer models. The combination markedly improved anti-tumor efficacy in vivo, with evidence of complete tumor clearance, prolongation of survival and induction of immunologic memory. Nature Publishing Group UK 2022-09-06 /pmc/articles/PMC9448789/ /pubmed/36068244 http://dx.doi.org/10.1038/s41523-022-00471-5 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Brief Communication
Pantelidou, Constantia
Jadhav, Heta
Kothari, Aditi
Liu, Renyan
Wulf, Gerburg M.
Guerriero, Jennifer L.
Shapiro, Geoffrey I.
STING agonism enhances anti-tumor immune responses and therapeutic efficacy of PARP inhibition in BRCA-associated breast cancer
title STING agonism enhances anti-tumor immune responses and therapeutic efficacy of PARP inhibition in BRCA-associated breast cancer
title_full STING agonism enhances anti-tumor immune responses and therapeutic efficacy of PARP inhibition in BRCA-associated breast cancer
title_fullStr STING agonism enhances anti-tumor immune responses and therapeutic efficacy of PARP inhibition in BRCA-associated breast cancer
title_full_unstemmed STING agonism enhances anti-tumor immune responses and therapeutic efficacy of PARP inhibition in BRCA-associated breast cancer
title_short STING agonism enhances anti-tumor immune responses and therapeutic efficacy of PARP inhibition in BRCA-associated breast cancer
title_sort sting agonism enhances anti-tumor immune responses and therapeutic efficacy of parp inhibition in brca-associated breast cancer
topic Brief Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9448789/
https://www.ncbi.nlm.nih.gov/pubmed/36068244
http://dx.doi.org/10.1038/s41523-022-00471-5
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