CPX-351 exploits the gut microbiota to promote mucosal barrier function, colonization resistance, and immune homeostasis

失调 肠道菌群 免疫学 殖民抵抗 生物 阿糖胞苷 柔红霉素 移植 免疫系统 髓样 造血干细胞移植 白血病 医学 微生物学 抗生素 内科学
作者
Giorgia Renga,Emilia Nunzi,Claudia Stincardini,Marilena Pariano,Matteo Puccetti,Giuseppe Pieraccini,Claudia Di Serio,Maurizio Fraziano,Noemi Poerio,Vasileios Oikonomou,Paolo Mosci,Enrico Garaci,Luana Fianchi,Livio Pagano,Luigina Romani
出处
期刊:Blood [American Society of Hematology]
卷期号:143 (16): 1628-1645 被引量:3
标识
DOI:10.1182/blood.2023021380
摘要

Abstract CPX-351, a liposomal combination of cytarabine plus daunorubicin, has been approved for the treatment of adults with newly diagnosed, therapy-related acute myeloid leukemia (AML) or AML with myelodysplasia-related changes, because it improves survival and outcome of patients who received hematopoietic stem cell transplant compared with the continuous infusion of cytarabine plus daunorubicin (referred to as “7 + 3” combination). Because gut dysbiosis occurring in patients with AML during induction chemotherapy heavily affects the subsequent phases of therapy, we have assessed whether the superior activity of CPX-351 vs “7 + 3” combination in the real-life setting implicates an action on and by the intestinal microbiota. To this purpose, we have evaluated the impact of CPX-351 and “7 + 3” combination on mucosal barrier function, gut microbial composition and function, and antifungal colonization resistance in preclinical models of intestinal damage in vitro and in vivo and fecal microbiota transplantation. We found that CPX-351, at variance with “7 + 3” combination, protected from gut dysbiosis, mucosal damage, and gut morbidity while increasing antifungal resistance. Mechanistically, the protective effect of CPX-351 occurred through pathways involving both the host and the intestinal microbiota, namely via the activation of the aryl hydrocarbon receptor–interleukin-22 (IL-22)–IL-10 host pathway and the production of immunomodulatory metabolites by anaerobes. This study reveals how the gut microbiota may contribute to the good safety profile, with a low infection-related mortality, of CPX-351 and highlights how a better understanding of the host-microbiota dialogue may contribute to pave the way for precision medicine in AML.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
1122完成签到,获得积分10
刚刚
刚刚
考拉完成签到,获得积分10
2秒前
烂漫耳机完成签到,获得积分20
3秒前
夏爽2023完成签到,获得积分10
4秒前
yc完成签到,获得积分20
4秒前
5秒前
佳敏完成签到,获得积分10
6秒前
Weining完成签到,获得积分10
6秒前
搜集达人应助金月桂采纳,获得10
7秒前
8秒前
8秒前
9秒前
李健的粉丝团团长应助swsn采纳,获得10
10秒前
卞卞发布了新的文献求助10
10秒前
10秒前
jenniesparrow发布了新的文献求助10
11秒前
温柔一刀完成签到,获得积分10
11秒前
11秒前
12秒前
1313131完成签到,获得积分10
13秒前
芝士蛋糕完成签到 ,获得积分10
13秒前
13秒前
13秒前
bkagyin应助鸣蜩阿六采纳,获得10
14秒前
14秒前
超级凉面发布了新的文献求助10
14秒前
wyt发布了新的文献求助10
15秒前
15秒前
完美世界应助须臾采纳,获得10
15秒前
rebeycca完成签到,获得积分10
15秒前
BEST发布了新的文献求助10
15秒前
JinZ发布了新的文献求助10
16秒前
任性成危发布了新的文献求助10
16秒前
18秒前
18秒前
18秒前
烟花应助怡然雁凡采纳,获得10
19秒前
19秒前
19秒前
高分求助中
Sustainability in Tides Chemistry 2800
The Young builders of New china : the visit of the delegation of the WFDY to the Chinese People's Republic 1000
Rechtsphilosophie 1000
Bayesian Models of Cognition:Reverse Engineering the Mind 888
Le dégorgement réflexe des Acridiens 800
Defense against predation 800
Very-high-order BVD Schemes Using β-variable THINC Method 568
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3135235
求助须知:如何正确求助?哪些是违规求助? 2786181
关于积分的说明 7776022
捐赠科研通 2442078
什么是DOI,文献DOI怎么找? 1298417
科研通“疑难数据库(出版商)”最低求助积分说明 625112
版权声明 600847