Low-dose irradiation of the gut improves the efficacy of PD-L1 blockade in metastatic cancer patients
The mechanisms governing the abscopal effects of local radiotherapy in cancer patients remain an open conundrum. Here, we show that off-target intestinal low-dose irradiation (ILDR) increases the clinical benefits of immune checkpoint inhibitors or chemotherapy in eight retrospective cohorts of canc...
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| Main Authors: | , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
March 10, 2025
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| In: |
Cancer cell
Year: 2025, Volume: 43, Issue: 3, Pages: 361-379.e10 |
| ISSN: | 1878-3686 |
| DOI: | 10.1016/j.ccell.2025.02.010 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.ccell.2025.02.010 Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S1535610825000625 
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| Author Notes: | Jianzhou Chen, Antonin Levy, Ai-Ling Tian, Xuehan Huang, Guoxin Cai, Marine Fidelle, Conrad Rauber, Pierre Ly, Eugénie Pizzato, Lisa Sitterle, Gianmarco Piccinno, Peng Liu, Sylvère Durand, Misha Mao, Liwei Zhao, Valerio Iebba, Hannah Felchle, Anne-Laure Mallard de La Varende, Julius Clemens Fischer, Simon Thomas, Tim F. Greten, Jennifer C. Jones, Cecilia Monge, Sandra Demaria, Silvia Formenti, Lorenzo Belluomini, Valeria Dionisi, Christophe Massard, Pierre Blanchard, Charlotte Robert, Clément Quevrin, Eloise Lopes, Céline Clémenson, Michele Mondini, Lydia Meziani, Yizhou Zhan, Chengbing Zeng, Qingxin Cai, Daphne Morel, Roger Sun, Pierre-Antoine Laurent, Monica Mangoni, Vanessa Di Cataldo, Chiara Arilli, Maike Trommer, Simone Wegen, Sebastian Neppl, Rachel P. Riechelmann, Marcos P. Camandaroba, Elson Santos Neto, Pierre-Edouard Fournier, Nicola Segata, Peter Holicek, Lorenzo Galluzzi, Aitziber Buqué, Carolina Alves Costa Silva, Lisa Derosa, Guido Kroemer, Chuangzhen Chen, Laurence Zitvogel, and Eric Deutsch |
| Summary: | The mechanisms governing the abscopal effects of local radiotherapy in cancer patients remain an open conundrum. Here, we show that off-target intestinal low-dose irradiation (ILDR) increases the clinical benefits of 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 (≥1 and ≤3 Gy) and on the metabolic and 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-L1 blockade, 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 first- or second-line immunotherapy in cancer patients. Prospective clinical trials are warranted to define optimal dosimetry and indications for ILDR to maximize its therapeutic potential. |
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| Item Description: | Gesehen am 07.05.2026 |
| Physical Description: | Online Resource |
| ISSN: | 1878-3686 |
| DOI: | 10.1016/j.ccell.2025.02.010 |