Intestinal low dose radiotherapy improves the efficacy of PD-L1 blockade in metastatic cancer patients

The abscopal effects of local radiotherapy (RT) supposedly rely on immunogenic cell death of cancer cells, that may pave the way to a better efficacy of immune checkpoint blockade (ICB). However, various combinational regimen of RT+ICB failed to show synergy across several advanced tumors. Here we show that off target intestinal low dose irradiation (ILDR) increased clinical benefit of ICB or chemotherapy in five independent cohorts of cancer patients across geographical sites and in tumor bearing mice. The abscopal effects of ILDR were dependent on the dosing of the off-target gut irradiation (between 1-3 grays), and on the baseline host-microbiota metabolic and immune interaction allowing CD8+ T cell activation without exhaustion. Prospective validation is warranted to better define ILDR target contours and dosimetry distribution, and maximize its possible therapeutic adjuvant value.