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Low-dose irradiation of the gut improves the efficacy of PD-L1 blockade in metastatic cancer patients
J. Chen, A. Levy, AL. Tian, X. Huang, G. Cai, M. Fidelle, C. Rauber, P. Ly, E. Pizzato, L. Sitterle, G. Piccinno, P. Liu, S. Durand, M. Mao, L. Zhao, V. Iebba, H. Felchle, AL. Mallard de La Varende, JC. Fischer, S. Thomas, TF. Greten, JC. Jones,...
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články
Perzistentní odkaz
https://www.medvik.cz/link/bmc25009528
Grantová podpora
R01 CA271915
NCI NIH HHS - United States
U54 CA274291
NCI NIH HHS - United States
ZIA BC011343
Intramural NIH HHS - United States
ZIA BC011503
Intramural NIH HHS - United States
- MeSH
- antigeny CD274 * antagonisté a inhibitory metabolismus imunologie MeSH
- CD8-pozitivní T-lymfocyty imunologie MeSH
- imunoterapie metody MeSH
- inhibitory kontrolních bodů * farmakologie terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- metastázy nádorů MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nádory imunologie radioterapie terapie MeSH
- retrospektivní studie MeSH
- senioři MeSH
- střeva patologie účinky záření MeSH
- střevní mikroflóra MeSH
- zvířata MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- senioři MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
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.
Cancer Signaling and Microenvironment Program Fox Chase Cancer Center Philadelphia PA 19111 2497 USA
Center for Molecular Medicine Cologne University of Cologne 50931 Cologne Germany
CICBT1428 Gustave Roussy Cancer Campus 94805 Villejuif France
Department of Clinical Oncology AC Camargo Cancer Center São Paulo 01509 900 Brazil
Department of Computational Cellular and Integrative Biology University of Trento 38123 Trento Italy
Department of Radiation Oncology AC Camargo Cancer Center São Paulo 01509 001 Brazil
Department of Radiation Oncology Gustave Roussy Cancer Campus 94805 Villejuif France
Department of Radiation Oncology University of Verona Hospital Trust 37126 Verona Italy
Department of Radiation Oncology Weill Cornell Medicine New York NY 10065 USA
Drug Development Department Gustave Roussy Cancer Campus 94805 Villejuif France
Faculté de Médecine Université Paris Saclay 94270 Kremlin Bicêtre France
Gustave Roussy Cancer Campus Clinicobiome 94805 Villejuif Cedex France
IEO Istituto Europeo di Oncologia IRCCS 20139 Milan Italy
IHU Méditerranée Infection 13005 Marseille France
Medical Physics Unit Azienda Ospedaliero Universitaria Careggi 50134 Florence Italy
Radiation Oncology Unit Azienda Ospedaliero Universitaria Careggi 50134 Florence Italy
Citace poskytuje Crossref.org
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- $a Chen, Jianzhou $u Gustave Roussy Cancer Campus (GRCC), Clinicobiome, 94805 Villejuif Cedex, France; Faculté de Médecine, Université Paris-Saclay, 94270 Kremlin-Bicêtre, France; Institut National de la Santé Et de la Recherche Médicale (INSERM) UMR 1015, Equipe Labellisée-Ligue Nationale contre le Cancer, 94805 Villejuif, France; Department of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shantou 515031, China
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- $a Low-dose irradiation of the gut improves the efficacy of PD-L1 blockade in metastatic cancer patients / $c J. Chen, A. Levy, AL. Tian, X. Huang, G. Cai, M. Fidelle, C. Rauber, P. Ly, E. Pizzato, L. Sitterle, G. Piccinno, P. Liu, S. Durand, M. Mao, L. Zhao, V. Iebba, H. Felchle, AL. Mallard de La Varende, JC. Fischer, S. Thomas, TF. Greten, JC. Jones, C. Monge, S. Demaria, S. Formenti, L. Belluomini, V. Dionisi, C. Massard, P. Blanchard, C. Robert, C. Quevrin, E. Lopes, C. Clémenson, M. Mondini, L. Meziani, Y. Zhan, C. Zeng, Q. Cai, D. Morel, R. Sun, PA. Laurent, M. Mangoni, V. Di Cataldo, C. Arilli, M. Trommer, S. Wegen, S. Neppl, RP. Riechelmann, MP. Camandaroba, ES. Neto, PE. Fournier, N. Segata, P. Holicek, L. Galluzzi, A. Buqué, C. Alves Costa Silva, L. Derosa, G. Kroemer, C. Chen, L. Zitvogel, E. Deutsch
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- $a 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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- $a Huang, Xuehan $u Department of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shantou 515031, China
- 700 1_
- $a Cai, Guoxin $u Gustave Roussy Cancer Campus (GRCC), Clinicobiome, 94805 Villejuif Cedex, France; Faculté de Médecine, Université Paris-Saclay, 94270 Kremlin-Bicêtre, France; Institut National de la Santé Et de la Recherche Médicale (INSERM) UMR 1015, Equipe Labellisée-Ligue Nationale contre le Cancer, 94805 Villejuif, France
- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
- $a Liu, Peng $u Metabolomics and Cell Biology Platforms, UMS AMMICa, Gustave Roussy Cancer Campus, 94805 Villejuif, France; Centre de Recherche des Cordeliers, INSERM U1138, Équipe Labellisée - Ligue Nationale contre le Cancer, Université Paris Cité, Sorbonne Université, 75006 Paris, France
- 700 1_
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- 700 1_
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- 700 1_
- $a Zhao, Liwei $u Metabolomics and Cell Biology Platforms, UMS AMMICa, Gustave Roussy Cancer Campus, 94805 Villejuif, France; Centre de Recherche des Cordeliers, INSERM U1138, Équipe Labellisée - Ligue Nationale contre le Cancer, Université Paris Cité, Sorbonne Université, 75006 Paris, France
- 700 1_
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- 700 1_
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- 700 1_
- $a Mallard de La Varende, Anne-Laure $u Gustave Roussy Cancer Campus (GRCC), Clinicobiome, 94805 Villejuif Cedex, France; Faculté de Médecine, Université Paris-Saclay, 94270 Kremlin-Bicêtre, France; Institut National de la Santé Et de la Recherche Médicale (INSERM) UMR 1015, Equipe Labellisée-Ligue Nationale contre le Cancer, 94805 Villejuif, France
- 700 1_
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- 700 1_
- $a Thomas, Simon $u Gustave Roussy Cancer Campus (GRCC), Clinicobiome, 94805 Villejuif Cedex, France; Faculté de Médecine, Université Paris-Saclay, 94270 Kremlin-Bicêtre, France; Institut National de la Santé Et de la Recherche Médicale (INSERM) UMR 1015, Equipe Labellisée-Ligue Nationale contre le Cancer, 94805 Villejuif, France
- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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