Figure 1. Schematic diagram of immunomodulatory effects of conventional fractionated radiation and high dose hypo-fractionated radiation therapy on anti-tumor response.

In conventional fractionated RT, small daily radiation doses cause tumor cells to either die by apoptosis or repair of radiation induced DNA damage and recover. High dose hypo-fractionated RT cause cancer cell death by necrosis. Uptake of apoptotic bodies by dendritic cells (DCs) can be tolerogenic while uptake of necrotic cells by dendritic cells is immunogenic. These DCs migrate to the draining lymph node and present tumor antigens to CD8⁺ T cells. These cross-primed CD8⁺ T cells migrate to the tumor and kill cancer cells that lead to tumor regression. As conventional RT is administered over prolonged period, radiation kills tumor infiltrating CD8⁺ T cells while sparing immunosuppressive cells such as MDSCs, Treg cells and TAMS. In contrast, in hypo-fractionated RT the radiation schedule is completed before CD8⁺ T cell infiltrate the tumor.