Lowdose Irradiation Of The Gut Improves The Efficacy Of Pdl1 Blockade In Metastatic Cancer Patients Jianzhou Chen by Jianzhou Chen, 1, 2, 3, 10, 36 Antonin Levy, 2, 5, 6, 36 Ai-ling Tian, Conrad Rauber, 1, 2, 3, 11 Pierre Ly, 1, 2, 3 Euge´ Nie Pizzato, 1, 2, 3 Sylve`re Durand, 7 Misha Mao, 7, 8, 25, 26 Liwei Zhao, 7, 8 Valerinne-laure Mallard De La Varende, 1, 2, 3 Julius C instant download after payment.

SUMMARYThe mechanisms governing the abscopal effects of local radiotherapy in cancer patients remain an openconundrum. Here, we show that off-target intestinal low-dose irradiation (ILDR) increases the clinical benefitsof immune checkpoint inhibitors or chemotherapy in eight retrospective cohorts of cancer patients and in tumor-bearing mice. The abscopal effects of ILDR depend on dosimetry (R1 and %3 Gy) and on the metabolicand immune host-microbiota interaction at baseline allowing CD8+ T cell activation without exhaustion.Various strains of Christensenella minuta selectively boost the anti-cancer efficacy of ILDR and PD-L1blockade, allowing emigration of intestinal PD-L1-expressing dendritic cells to tumor-draining lymph nodes.An interventional phase 2 study provides the proof-of-concept that ILDR can circumvent resistance to firstor second-line immunotherapy in cancer patients. Prospective clinical trials are warranted to define optimaldosimetry and indications for ILDR to maximize its therapeutic potential.