Radiation therapy (RT) has been shown to increase tumor immunogenicity, supporting synergy between RT and immunotherapy. We propose that the therapeutic ratio of proton FLASH RT could be further improved beyond reported studies in the literature of normal tissue sparing by capitalizing on RT induced anti-tumor immunity. This would lead to enhanced tumor-cell targeting by the immune system and support combinations of FLASH RT and immunotherapy. We propose to investigate the role of FLASH RT to modulate key immunogenic and immune suppressive markers in tumors and normal tissue. We will investigate in vitro the extent to which FLASH RT influences antigen processing and presentation, micronuclei formation and rupture, and type-I interferon signaling in breast cancer and normal breast cell lines. This work has the potential to establish fundamental evidence that FLASH RT leads to immunogenic signaling in tumors, or alters signaling in healthy cells, which could be exploited to improve the care of breast patients with radiation-resistant disease through a combination of FLASH RT and immunotherapeutics.