秦环龙团队:大肠癌中的“坏”细菌,或能在免疫治疗中发挥“好”作用
  • 分析41名接受PD-1阻断治疗的结直肠癌(CRC)患者,发现具核梭杆菌(Fn)水平较高的患者有更好的治疗效果;
  • 在多种CRC小鼠模型中,Fn可增强PD-L1阻断治疗的抗肿瘤效果、延长生存期,并使对PD-L1阻断治疗不应答的小鼠产生应答;
  • 机制上,Fn可活化STING信号通路诱导CRC细胞表达PD-L1,并增加IFN-γ+CD8+肿瘤浸润淋巴细胞的积累,从而提高肿瘤对PD-L1阻断治疗的敏感性;
  • 在CRC患者衍生的类器官中,暴露于Fn可提高对PD-L1阻断治疗的应答。
主编推荐语
mildbreeze
很多研究显示,结直肠癌(CRC)中的具核梭杆菌是促癌的“坏”细菌,能增强CRC的化疗耐药性、抑制免疫。同济大学附属上海第十人民医院秦环龙和蔚青作为共同通讯作者在Signal Transduction and Targeted Therapy上发表的一项最新研究却发现,具核梭杆菌对CRC治疗可能也有“好”的一面——增强抗PD-L1免疫治疗的效果,并阐释了相关作用机制。这些发现揭示了具核梭杆菌在CRC免疫治疗中的新作用,并为临床预测PD-1/PD-L1阻断治疗的疗效提供了潜在的生物标志物。
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Fusobacterium nucleatum enhances the efficacy of PD-L1 blockade in colorectal cancer

具核梭杆菌增强PD-L1阻断治疗在结直肠癌中的疗效

10.1038/s41392-021-00795-x

2021-11-19, Article

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Given that only a subset of patients with colorectal cancer (CRC) benefit from immune checkpoint therapy, efforts are ongoing to identify markers that predict immunotherapeutic response. Increasing evidence suggests that microbes influence the efficacy of cancer therapies. Fusobacterium nucleatum induces different immune responses in CRC with different microsatellite-instability (MSI) statuses. Here, we investigated the effect of F. nucleatum on anti-PD-L1 therapy in CRC. We found that high F. nucleatum levels correlate with improved therapeutic responses to PD-1 blockade in patients with CRC. Additionally, F. nucleatum enhanced the antitumor effects of PD-L1 blockade on CRC in mice and prolonged survival. Combining F. nucleatum supplementation with immunotherapy rescued the therapeutic effects of PD-L1 blockade. Furthermore, F. nucleatum induced PD-L1 expression by activating STING signaling and increased the accumulation of interferon-gamma (IFN-γ)+ CD8+ tumor-infiltrating lymphocytes (TILs) during treatment with PD-L1 blockade, thereby augmenting tumor sensitivity to PD-L1 blockade. Finally, patient-derived organoid models demonstrated that increased F. nucleatum levels correlated with an improved therapeutic response to PD-L1 blockade. These findings suggest that F. nucleatum may modulate immune checkpoint therapy for CRC.

First Authors:
Yaohui Gao,Dexi Bi,Ruting Xie

Correspondence Authors:
Qing Wei,Huanlong Qin

All Authors:
Yaohui Gao,Dexi Bi,Ruting Xie,Man Li,Jing Guo,Hu Liu,Xianling Guo,Juemin Fang,Tingting Ding,Huiyuan Zhu,Yuan Cao,Meichun Xing,Jiayi Zheng,Qing Xu,Qian Xu,Qing Wei,Huanlong Qin

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