Ionizing radiation (RT) induces an anti-tumor immune response within the tumor through the generation of inflammatory mediators including cytosolic dsDNA, HMGB1, ATP, calreticulin (CRT) and Hsp70 within the tumor cells. These molecules activate the resident immune cells such as macrophages to secrete a series of cytokines/chemokines including IL-1 and TNF-α, which further recruits more macrophages to the tumor site. Activated macrophages and DCs migrate to the lymphoid tissues bearing tumor antigens, where they present them to T cells. Activated T cells then re-enter the circulation and return to the tumor where they target malignant cells. However, the outcome of the response is in part determined by the ability of the T cell response to the microenvironment. If the malignant cells are completely eradicated, macrophages help restore normal tissue homeostasis by supporting angiogenesis and matrix remodeling. If there is an insufficient immune response, macrophages still attempt to restore tissue to its normal state but in so doing inadvertently support tumor regrowth.