Radiation therapy for cancer treatment is delivered more or less in the same mode during the past 100 years. Low dose (2 Gy) fractions are given daily until a high target dose (60-70 Gy) is achieved. This treatment regime aims at eradicating the tumour by radiation induced cancer cell death. But traditional fractionated radiation therapy also decreases the number of radiation sensitive T-cells (CD3+, CD4+, and CD8+) in the tumour and thus prohibits immunogenic cell death. Several pre-clinical studies show that radiation therapy given by hypo-fractionation dramatically enhances the effect of otherwise non-effective immune-therapy. This opens up the possibility for an alternate cancer therapy regime using radiation in co-operation with immune therapy, instead of counteracting as in conventional fractionated radiation therapy regimes. This review summarizes the effects of various fractionation modes of radiation on the tumour and various immune cells: CD4+ and CD8+ T-cells, Treg, natural killer (NK) cells and dendritic cells (DCs). A number of pre-clinical studies which demonstrate the enhanced therapeutic response of malignant tumours to various combinations of immunotherapy (IMU) with single fraction or hypo-fractionated radiation therapy (RT) are reviewed. The clinical trials of combining immune therapy and radiation therapy carried out so far have been performed by using conventional radiation therapy with sparse effect. Clinical studies of combining established IMU regimes with a single 8 Gy fraction RT could open up the possibility for a deeper co-operation between biology and physics. This therapeutic co-operative regime may also reduce the probability of relapse, and if relapse occurs the treatment can be repeated.
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