Background
Radiotherapy (RT) effectively kills cancer cells by inducing DNA damage and by provoking anti-tumor immune responses, which can be further increased when combined with immunotherapy (IT). The patients’ capacity to induce effective anti-cancer immune responses upon RT/IT combination treatment depends on an optimal functioning immune system and specific dietary ingredients have been recognized to support the immune system. Therefore, we aim to investigate which mixture of dietary ingredients is able to strengthen immune fitness and boosts the efficacy of RT/IT combination treatment.

Methods
Immune-competent BALB/cOla Hsd mice (n=60) were injected subcutaneously with 1,5x10⁶ CT-26 colon cancer cells and randomized across 1 control diet (AIN93M) and 4 iso-caloric AIN93M based test diets. When the tumor reached a starting volume (SV) of ±200mm³ sub-curative RT (5 consecutive days 2,33Gy) and IT (anti-PD-L1, 10mg/kg Q.O.D. for 5 times) treatment started. Mice were sacrificed when a tumor volume of 4xSV (±800mm³) was reached, or when for 60 days no tumor was palpable. Throughout the experiment, body weight and food intake were monitored and at autopsy several tissues were collected.

Results
Body weight and food intake were comparable over time between the different diets, in line with their iso-caloric composition. Depending on the diet, RT/IT combination treatment induced long-lasting curative responses ranging from 0% to 33% of the mice. Surprisingly cox regression analysis, based on progression free survival, indicated best outcome in the control group. Cured mice receiving the control diet had smaller spleens compared to non-cured mice (p=0,0008) and similar trends were observed comparing the cured and non-cured mice receiving the test diets. 

Conclusion
None of the investigated mixtures of dietary ingredients improved the efficacy of RT/IT combination treatment. Future research will focus on understanding underlying mechanisms in order to design novel ingredient mixtures to improve outcome.