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

Chen, Jianzhou; Levy, Antonin; Tian, Ai-Ling; Huang, Xuehan; Cai, Guoxin; Fidelle, Marine; Rauber, Conrad; Ly, Pierre; Pizzato, Eugénie; Sitterle, Lisa; Piccinno, Gianmarco; Liu, Peng; Durand, Sylvère; Mao, Misha; Zhao, Liwei; Iebba, Valerio; Felchle, Hannah; Mallard de La Varende, Anne-Laure; Fischer, Julius Clemens; Thomas, Simon; Greten, Tim F; Jones, Jennifer C; Monge, Cecilia; Demaria, Sandra; Formenti, Silvia; Belluomini, Lorenzo; Dionisi, Valeria; Massard, Christophe; Blanchard, Pierre; Robert, Charlotte; Quevrin, Clément; Lopes, Eloise; Clémenson, Céline; Mondini, Michele; Meziani, Lydia; Zhan, Yizhou; Zeng, Chengbing; Cai, Qingxin; Morel, Daphne; Sun, Roger; Laurent, Pierre-Antoine; Mangoni, Monica; Di Cataldo, Vanessa; Arilli, Chiara; Trommer, Maike; Wegen, Simone; Neppl, Sebastian; Riechelmann, Rachel P; Camandaroba, Marcos P; Neto, Elson Santos; Fournier, Pierre-Edouard; Segata, Nicola; Holicek, Peter; Galluzzi, Lorenzo; Buqué, Aitziber; Alves Costa Silva, Carolina; Derosa, Lisa; Kroemer, Guido; Chen, Chuangzhen; Zitvogel, Laurence; Deutsch, Eric

doi:10.1016/j.ccell.2025.02.010

Title

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

Publication Date

2025-03-10

Author(s)

Chen, Jianzhou

Levy, Antonin

Tian, Ai-Ling

Huang, Xuehan

Cai, Guoxin

Fidelle, Marine

Rauber, Conrad

Ly, Pierre

Pizzato, Eugénie

Sitterle, Lisa

Piccinno, Gianmarco

Liu, Peng

Durand, Sylvère

Mao, Misha

Zhao, Liwei

Iebba, Valerio

Felchle, Hannah

Mallard de La Varende, Anne-Laure

Fischer, Julius Clemens

Thomas, Simon

Greten, Tim F

Jones, Jennifer C

Monge, Cecilia

Demaria, Sandra

Formenti, Silvia

Belluomini, Lorenzo

Dionisi, Valeria

Massard, Christophe

Blanchard, Pierre

Robert, Charlotte

Quevrin, Clément

Lopes, Eloise

Clémenson, Céline

Mondini, Michele

Meziani, Lydia

Zhan, Yizhou

Zeng, Chengbing

Cai, Qingxin

Morel, Daphne

Sun, Roger

Laurent, Pierre-Antoine

Mangoni, Monica

Di Cataldo, Vanessa

Arilli, Chiara

Trommer, Maike

Wegen, Simone

Neppl, Sebastian

Riechelmann, Rachel P

Camandaroba, Marcos P

Neto, Elson Santos

Fournier, Pierre-Edouard

Segata, Nicola

Holicek, Peter

Galluzzi, Lorenzo

Buqué, Aitziber

Alves Costa Silva, Carolina

Derosa, Lisa

Kroemer, Guido

Chen, Chuangzhen

Zitvogel, Laurence

Deutsch, Eric

Subject

Christensenella minuta

bile acids

cancer

dendritic cells

gut microbiota

metabolomics

radiotherapy

tumor immunosurveillance

Type of document

Journal Article

OrcId

#PLACEHOLDER_PARENT_METADATA_VALUE#

DOI

10.1016/j.ccell.2025.02.010

Abstract

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.

Link

link

Citation

Cancer cell 2025-03-10; 43(3)

Jornal Title

Cancer cell

ISSN

1878-3686

Austin Health

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