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

Autor: Constantia Pantelidou, Heta Jadhav, Aditi Kothari, Renyan Liu, Gerburg M. Wulf, Jennifer L. Guerriero, Geoffrey I. Shapiro
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: npj Breast Cancer, Vol 8, Iss 1, Pp 1-6 (2022)
Druh dokumentu: article
ISSN: 2374-4677
DOI: 10.1038/s41523-022-00471-5
Popis: Abstract 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.
Databáze: Directory of Open Access Journals
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