Resumen
Trastuzumab and radiation are used clinically to treat HER2-overexpressing breast cancers; however, the mechanistic synergy of anti-HER2 and radiation therapy has not been investigated. In this study, we identify that a subtherapeutic dose of trastuzumab sensitizes the tumor microenvironment to fractionated radiation. This results in longitudinal sustained response by triggering a state of innate immune activation through reduced DNA damage repair and increased tumor oxygenation. As positron emission tomography imaging can be used to longitudinally evaluate changes in tumor hypoxia, synergy of combination therapies is the result of both cellular and molecular changes in the tumor microenvironment.