微生物组调节在小鼠多发性骨髓瘤中通过免疫检查点阻塞诱导的疗效和毒性
Laura Lucia Cogrossi1,2, Anna Policastro1, Paola Zordan1
1Cellular immunology Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS Ospedale San Raffaele, Milan, Italy.
Nature communications
|November 25, 2025
概括
肠道细菌Prevotella melaninogenica及其代谢物丁酸盐可以延缓多发性骨髓瘤的进展. 这种方法可以通过调节肠道微生物群和短链脂肪酸,为血细胞疾病提供新的治疗方法.
科学领域:
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
- 在瘤学瘤学.
背景情况:
- 燃烧的多发性骨髓瘤 (SMM) 可以发展为危及生命的多发性骨髓瘤 (MM).
- 肠道微生物群和T助手-17 (Th17) 细胞与MM的发展有关,但机制尚不清楚.
- 了解这些机制对于开发有效疗法至关重要.
研究的目的:
- 调查Prevotella melaninogenica在SMM向MM的进展中的作用.
- 阐明肠道微生物群影响髓瘤发育的机制.
- 探索针对肠道微生物群及其代谢物的潜在治疗策略.
主要方法:
- 将Prevotella melaninogenica给具有SMM类表型的转基因小鼠.
- 对短链脂肪酸 (SCFA) 生产的分析.
- 流细胞测量以评估树突细胞和Th17细胞表型.
- 评估免疫疗法 (抗PD-L1,抗TIGIT) 的协同效应.
- 评估IL-17介导的皮肤病变.
主要成果:
- 在小鼠中,P. melaninogenica的使用延迟了从SMM到MM的进展.
- P. melaninogenica增加了SCFA的产生,防止了树突细胞中的亲Th17细胞表型.
- 在接受治疗的小鼠的骨髓中减少了Th17细胞的积累.
- 梅拉尼诺基尼卡和丁酸盐与免疫疗法协同作用,通过调节T细胞反应来抑制骨髓瘤.
- P. melaninogenica减弱的IL-17介导的皮肤病变.
结论:
- 肠道微生物群调节,特别是P. melaninogenica,可以延迟多发性骨髓瘤的进展.
- 施用SCFA可以防止Th17细胞驱动骨髓瘤的发展.
- 涉及肠道微生物群,SCFA和免疫治疗的联合策略显示出治疗血细胞失色症的前景.
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