Low-dose irradiation of the gut improves the efficacy of PD-L1 blockade in metastatic cancer patients
| Title: | Low-dose irradiation of the gut improves the efficacy of PD-L1 blockade in metastatic cancer patients |
|---|---|
| Authors: | Chen J.; Levy A.; Tian A. -L.; Huang X.; Cai G.; Fidelle M.; Rauber C.; Ly P.; Pizzato E.; Sitterle L.; Piccinno G.; Liu P.; Durand S.; Mao M.; Zhao L.; Iebba V.; Felchle H.; Mallard de La Varende A. -L.; Fischer J. C.; Thomas S.; Greten T. F.; Jones J. C.; Monge C.; Demaria S.; Formenti S.; Belluomini L.; Dionisi V.; Massard C.; Blanchard P.; Robert C.; Quevrin C.; Lopes E.; Clemenson C.; Mondini M.; Meziani L.; Zhan Y.; Zeng C.; Cai Q.; Morel D.; Sun R.; Laurent P. -A.; Mangoni M.; Di Cataldo V.; Arilli C.; Trommer M.; Wegen S.; Neppl S.; Riechelmann R. P.; Camandaroba M. P.; Neto E. S.; Fournier P. -E.; Segata N.; Holicek P.; Galluzzi L.; Buque A.; Alves Costa Silva C.; Derosa L.; Kroemer G.; Chen C.; Zitvogel L.; Deutsch E. |
| Contributors: | Chen, J.; Levy, A.; Tian, A. -L.; Huang, X.; Cai, G.; Fidelle, M.; Rauber, C.; Ly, P.; Pizzato, E.; Sitterle, L.; Piccinno, G.; Liu, P.; Durand, S.; Mao, M.; Zhao, L.; Iebba, V.; Felchle, H.; Mallard De La Varende, A. -L.; Fischer, J. C.; Thomas, S.; Greten, T. F.; Jones, J. C.; Monge, C.; Demaria, S.; Formenti, S.; Belluomini, L.; Dionisi, V.; Massard, C.; Blanchard, P.; Robert, C.; Quevrin, C.; Lopes, E.; Clemenson, C.; Mondini, M.; Meziani, L.; Zhan, Y.; Zeng, C.; Cai, Q.; Morel, D.; Sun, R.; Laurent, P. -A.; Mangoni, M.; Di Cataldo, V.; Arilli, C.; Trommer, M.; Wegen, S.; Neppl, S.; Riechelmann, R. P.; Camandaroba, M. P.; Neto, E. S.; Fournier, P. -E.; Segata, N.; Holicek, P.; Galluzzi, L.; Buque, A.; Alves Costa Silva, C.; Derosa, L.; Kroemer, G.; Chen, C.; Zitvogel, L.; Deutsch, E. |
| Publication Year: | 2025 |
| Collection: | Università degli studi di Trieste: ArTS (Archivio della ricerca di Trieste) |
| Subject Terms: | bile acid; cancer; Christensenella minuta; dendritic cell; gut microbiota; metabolomic; radiotherapy; tumor immunosurveillance |
| Description: | 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. |
| Document Type: | article in journal/newspaper |
| Language: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/40068595; volume:43; issue:3; firstpage:361; lastpage:379.e.10; numberofpages:30; journal:CANCER CELL; https://hdl.handle.net/11368/3118243; https://www.sciencedirect.com/science/article/pii/S1535610825000625?via=ihub |
| DOI: | 10.1016/j.ccell.2025.02.010 |
| Availability: | https://hdl.handle.net/11368/3118243; https://doi.org/10.1016/j.ccell.2025.02.010; https://www.sciencedirect.com/science/article/pii/S1535610825000625?via=ihub |
| Rights: | info:eu-repo/semantics/openAccess ; license:Creative commons ; license uri:http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Accession Number: | edsbas.B231C2A0 |
| Database: | BASE |