STING agonism enhances anti-tumor immune responses and therapeutic efficacy of PARP inhibition in BRCA-associated breast cancer
oleh: Constantia Pantelidou, Heta Jadhav, Aditi Kothari, Renyan Liu, Gerburg M. Wulf, Jennifer L. Guerriero, Geoffrey I. Shapiro
| Format: | Article |
|---|---|
| Diterbitkan: | Nature Portfolio 2022-09-01 |
Deskripsi
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.