Low-dose irradiation of the gut improves the efficacy of PD-L1 blockade in metastatic cancer patients

DOI: 10.1016/j.ccell.2025.02.010 Publication Date: 2025-03-10T14:42:39Z
ABSTRACT
Highlights•Off-target ILDR synergizes with anti-PD-L1 to eradicate non-irradiated tumors•The abscopal effects of depend on dosimetry (≥1 and ≤3 Gy) volume•Gut composition governs the combined anti-PD-L1•ILDR Christensenellaceae influence emigration intestinal mregDC TdLNSummaryThe mechanisms governing local radiotherapy in cancer patients remain an open conundrum. Here, we show that off-target low-dose irradiation (ILDR) increases clinical benefits immune checkpoint inhibitors or chemotherapy eight retrospective cohorts tumor-bearing mice. The metabolic host-microbiota interaction at baseline allowing CD8+ T cell activation without exhaustion. Various strains Christensenella minuta selectively boost anti-cancer efficacy PD-L1 blockade, PD-L1-expressing dendritic cells tumor-draining lymph nodes. An interventional phase 2 study provides proof-of-concept can circumvent resistance first- second-line immunotherapy patients. Prospective trials are warranted define optimal indications for maximize its therapeutic potential.Graphical abstract
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