Abstract B083: Centrosome De-clustering as an Immune-Modulating Radiosensitizer: Implications for Enhancing RT-Induced Innate Immunity

Abstract Radiotherapy (RT) increases the number of centrosomes in cancer cells, leading to centrosome clustering that supports bipolar mitosis and tumor cell proliferation. Targeting centrosome clustering has emerged as a potential strategy to enhance RT effects in breast cancer cells. However, the role of centrosome de-clustering in activating innate immunity in response to RT is still unclear. Our study demonstrates that centrosome de-clustering in irradiated cancer cells influences the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING)-mediated immune response in monocytes and macrophages after co-culture. While centrosome de-clustering heightened mitotic errors and increased cytosolic dsDNA in breast cancer cells post-irradiation, it did not directly activate the cGAS-STING pathway in the cancer cells themselves. Notably, it triggered this pathway in human monocytes and mouse macrophages following co-culture with the irradiated cancer cells. These findings provide the first evidence that centrosome de-clustering in irradiated breast cancer cells promotes innate immune activation in tumor-associated immune cells, offering insights for potential immunotherapy strategies. Citation Format: JAE SUNG KIM. Centrosome De-clustering as an Immune-Modulating Radiosensitizer: Implications for Enhancing RT-Induced Innate Immunity [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr B083.