Background
Radiotherapy (RT) effectively kills cancer cells by inducing DNA damage and provokes anti-tumor immune responses, which can be enhanced upon combination with immunotherapy (IT). Effective anti-cancer immune responses induced by RT/IT combination treatment are dependent on an optimal functioning immune system and specific dietary ingredients have been recognized to support the immune system. Therefore, we aim to investigate whether dietary composition affects RT/IT combination treatment efficacy.

Methods
Immune-competent BALB/cOla Hsd mice (n=60) were injected subcutaneously with 1,5x10⁶ CT-26 colon cancer cells and randomized across 5 iso-caloric AIN93M-based test diets. At a tumor volume of 238,0 +/- 67,2 mm³ (starting volume (SV)), sub-curative RT (5 consecutive days of 2,33Gy) and IT (anti-PD-L1, 10mg/kg Q2Dx5) treatment started. Endpoint was defined as a tumor volume of 4xSV or 60 days when no palpable tumor present. Throughout the experiment, body weight and food intake were monitored. At pre-treatment, post-treatment and endpoint grip strength tests and whole body CT-scans were performed.

Results
Depending on the diet, RT/IT combination treatment induced long-lasting curative responses ranging from 0%-33% of the mice. Cox regression analysis, based on progression free survival, indicated statistically significant differences between the different diets. Body weight and food intake were comparable over time between the diets, similarly as grip strength tests results and auto-calculated hind leg muscle masses and volumes. Likewise, hind leg wet muscle masses at autopsy were also not significantly different. Lastly, non-cured mice had larger spleens compared to cured mice and in line with these data non-cured mice had elevated systemic pentraxin-2 levels compared to cured mice. Systemic IL-8 levels were not significantly different between cured and non-cured mice.

Conclusion
These data show that dietary composition affects the efficacy of RT/IT combination treatment.