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DOI 10.1016/j.ccell.2025.02.010

Медицинская библиотека · Cancer cell · 2025

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

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Аннотация

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.

Для цитирования: 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. Low-dose irradiation of the gut improves the efficacy of PD-L1 blockade in metastatic cancer patients.. Cancer cell. 2025. DOI: 10.1016/j.ccell.2025.02.010.

Предметные рубрики MeSH

AnimalsMiceHumansImmune Checkpoint InhibitorsB7-H1 AntigenNeoplasmsGastrointestinal MicrobiomeFemaleRetrospective StudiesMaleCD8-Positive T-LymphocytesIntestinesMice, Inbred C57BLImmunotherapy
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