Abstract 2565: Type I interferons enhance chemosensitivity of breast cancer by inhibiting DNA repair

Abstract

Abstract Type I interferons (IFNs) are known to have antineoplastic effects against several tumors by stimulating anticancer immune response. In this study, we identified a novel function of type I IFNs in DNA repair, which enhanced chemosensitivity in breast cancer cells. We investigated that IFNα and IFNβ inhibited both non-homologous recombination and homologous recombination double strand breaks repair. Moreover, IFNs accelerated the release of DNA into the cytoplasm in response to DNA damaging agent, doxorubicin. In agreement, IFNs synergistically activated DNA damage-induced STING pathway and increased the production of chemokines, CCL5 and CXCL11. In agreement, IFNβ greatly increased the sensitivity of cells to doxorubicin-induced suppression of cell survival. This sensitizing effect of IFNβ was also supported by in vivo xenograft experiments. Thus, combination therapy with chemotherapeutic agents and IFNs may be effective against breast cancer, particularly in patients with defective in DNA damage response pathways. The downstream effectors that modulate the effect of IFNs should be investigated as predictive biomarker in the treatment of breast cancer. Citation Format: Na-Lee Ka, Ga Young Lim, Mi-Ock Lee. Type I interferons enhance chemosensitivity of breast cancer by inhibiting DNA repair [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2565.