Traditional factors of DNA damage and tumor cell kill, described by the "4 R's" of radiobiology (Reassortment, Reoxygenation, Repair, and Repopulation) fall short in explaining the role of immunity in hosts treated with radiotherapy. We propose a "5th R," (immune-mediated) Rejection, which recognizes the contribution of the immune system to the antineoplastic effects of radiotherapy.
Keywords: ATP; CTLA4; CXCL16; CXCR6; HMGB1; NKG2D; RAE-1; abscopal effect; calreticulin; immunogenic cell death; ionizing irradiation; ipilimumab; radiobiology.