Fusobacterium nucleatum enhances the efficacy of PD-L1 blockade in colorectal cancer

Abstract 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 nuc...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Medicine R Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/590c41649479464395ada50dedae6436
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spelling	oai:doaj.org-article:590c41649479464395ada50dedae64362021-11-21T12:07:04ZFusobacterium nucleatum enhances the efficacy of PD-L1 blockade in colorectal cancer10.1038/s41392-021-00795-x2059-3635https://doaj.org/article/590c41649479464395ada50dedae64362021-11-01T00:00:00Zhttps://doi.org/10.1038/s41392-021-00795-xhttps://doaj.org/toc/2059-3635Abstract 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.Yaohui GaoDexi BiRuting XieMan LiJing GuoHu LiuXianling GuoJuemin FangTingting DingHuiyuan ZhuYuan CaoMeichun XingJiayi ZhengQing XuQian XuQing WeiHuanlong QinNature Publishing GrouparticleMedicineRBiology (General)QH301-705.5ENSignal Transduction and Targeted Therapy, Vol 6, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Biology (General) QH301-705.5
spellingShingle	Medicine R Biology (General) QH301-705.5 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 Fusobacterium nucleatum enhances the efficacy of PD-L1 blockade in colorectal cancer
description	Abstract 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.
format	article
author	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
author_facet	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
author_sort	Yaohui Gao
title	Fusobacterium nucleatum enhances the efficacy of PD-L1 blockade in colorectal cancer
title_short	Fusobacterium nucleatum enhances the efficacy of PD-L1 blockade in colorectal cancer
title_full	Fusobacterium nucleatum enhances the efficacy of PD-L1 blockade in colorectal cancer
title_fullStr	Fusobacterium nucleatum enhances the efficacy of PD-L1 blockade in colorectal cancer
title_full_unstemmed	Fusobacterium nucleatum enhances the efficacy of PD-L1 blockade in colorectal cancer
title_sort	fusobacterium nucleatum enhances the efficacy of pd-l1 blockade in colorectal cancer
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/590c41649479464395ada50dedae6436
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Fusobacterium nucleatum enhances the efficacy of PD-L1 blockade in colorectal cancer

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