Radio-Immunology of Ablative Radiation

High ablative doses of radiation can be safely delivered to tumors using stereotactic radiosurgery (SRS), stereotactic body radiation therapy (SBRT), or stereotactic ablative radiotherapy (SABR) with local control rates similar to surgery. The immunological impact of various radiation schedules, from conventional protracted fractionation to short courses of stereotactic radiation, is multifactorial and sometimes counterproductive to tumor clearance by immune effector cells. Ablative radiation has the potential to serve as a potent source of tumor-derived antigens and release of danger-associated molecular pattern (DAMP) ligands for induction of antitumoral immunity and tumor cell immunomodulation. The tumor microenvironment is often an immune-privileged site with diminished immune responses and increased immune suppression. In this chapter, we discuss the immunological consequences of radiosurgery and present a roadmap for combining ablative radiation with immunotherapy with careful consideration of radiation dose and fractionation, types of immunotherapeutic agents, and the baseline immunophenotype of the tumor. These treatment modalities can be tailored to patients based on their disease phenotype for increased local and systemic control.