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基于PD-1的免疫疗法对表皮瘤的疗效受到肠道微生物组的影响

Bertrand Routy^1,2,3, Emmanuelle Le Chatelier⁴, Lisa Derosa^1,2,3

¹Gustave Roussy Cancer Campus (GRCC), Villejuif, France.

Science (New York, N.Y.)

|November 4, 2017

概括

肠道微生物群影响癌症治疗. 特定的细菌如Akkermansia muciniphila可以恢复免疫检查点抑制剂 (PD-1阻断剂) 的有效性.

科学领域:

免疫学
癌症学
微生物组研究

背景情况:

针对PD-1/PD-L1轴的免疫检查点抑制剂 (ICI) 对一些癌症患者提供临床益处.
对ICI的原发性耐药性是癌症治疗中的一个重大挑战.
人们越来越认识到肠道微生物群对ICI有效性的作用.

研究的目的:

研究肠道微生物组合对PD-1阻断疗法的原发性耐药性的影响.
探索调节肠道微生物组以提高ICI的有效性.

主要方法:

在接受ICI治疗的癌症患者中分析肠道微生物组合.
在无细菌或接受抗生素治疗的小鼠中使用便微生物移植 (FMT) 的研究.
用特定的细菌物种 (Akkermansia muciniphila) 进行口服补充.
在小鼠模型中评估抗瘤效应和免疫细胞透.

主要成果:

肠道微生物组的异常与ICI的原发性耐药性有关.
抗生素治疗减少了ICI的临床益处.
接受ICI治疗的患者的FMT恢复了小鼠的抗瘤作用,而没有反应的患者的FMT则没有.
与临床反应相关的Akkermansia muciniphila丰度.
口服A. muciniphila补充剂恢复了与非响应微生物群结合的小鼠的ICI疗效.

结论:

肠道微生物组失调有助于对PD-1封锁的初级抵抗.
在调解PD-1阻断的有效性方面,Akkermansia muciniphila发挥着至关重要的作用.
调节肠道微生物群,特别是A. muciniphila,是克服ICI耐药性的潜在策略.

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