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Intratumoral accumulation of gut microbiota facilitates CD47-based immunotherapy via STING signaling

Most studies focus on how intestinal microbiota influence cancer immunotherapy through activating gut immunity. However, immunotherapies related to innate responses such as CD47 blockade rely on the rapid immune responses within the tumor microenvironment. Using one defined anaerobic gut microbiota...

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Autores principales: Shi, Yaoyao, Zheng, Wenxin, Yang, Kaiting, Harris, Katharine G., Ni, Kaiyuan, Xue, Lai, Lin, Wenbin, Chang, Eugene B., Weichselbaum, Ralph R., Fu, Yang-Xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201921/
https://www.ncbi.nlm.nih.gov/pubmed/32142585
http://dx.doi.org/10.1084/jem.20192282
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author Shi, Yaoyao
Zheng, Wenxin
Yang, Kaiting
Harris, Katharine G.
Ni, Kaiyuan
Xue, Lai
Lin, Wenbin
Chang, Eugene B.
Weichselbaum, Ralph R.
Fu, Yang-Xin
author_facet Shi, Yaoyao
Zheng, Wenxin
Yang, Kaiting
Harris, Katharine G.
Ni, Kaiyuan
Xue, Lai
Lin, Wenbin
Chang, Eugene B.
Weichselbaum, Ralph R.
Fu, Yang-Xin
author_sort Shi, Yaoyao
collection PubMed
description Most studies focus on how intestinal microbiota influence cancer immunotherapy through activating gut immunity. However, immunotherapies related to innate responses such as CD47 blockade rely on the rapid immune responses within the tumor microenvironment. Using one defined anaerobic gut microbiota to track whether microbiota interact with host immunity, we observed that Bifidobacterium facilitates local anti-CD47 immunotherapy on tumor tissues through the capacity to accumulate within the tumor microenvironment. Systemic administration of Bifidobacterium leads to its accumulation within the tumor and converts the nonresponder mice into responders to anti-CD47 immunotherapy in a stimulator of interferon genes (STING)– and interferon-dependent fashion. Local delivery of Bifidobacterium potently stimulates STING signaling and increases cross-priming of dendritic cells after anti-CD47 treatment. Our study identifies the mechanism by which gut microbiota preferentially colonize in tumor sites and facilitate immunotherapy via STING signaling.
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spelling pubmed-72019212020-11-04 Intratumoral accumulation of gut microbiota facilitates CD47-based immunotherapy via STING signaling Shi, Yaoyao Zheng, Wenxin Yang, Kaiting Harris, Katharine G. Ni, Kaiyuan Xue, Lai Lin, Wenbin Chang, Eugene B. Weichselbaum, Ralph R. Fu, Yang-Xin J Exp Med Brief Definitive Report Most studies focus on how intestinal microbiota influence cancer immunotherapy through activating gut immunity. However, immunotherapies related to innate responses such as CD47 blockade rely on the rapid immune responses within the tumor microenvironment. Using one defined anaerobic gut microbiota to track whether microbiota interact with host immunity, we observed that Bifidobacterium facilitates local anti-CD47 immunotherapy on tumor tissues through the capacity to accumulate within the tumor microenvironment. Systemic administration of Bifidobacterium leads to its accumulation within the tumor and converts the nonresponder mice into responders to anti-CD47 immunotherapy in a stimulator of interferon genes (STING)– and interferon-dependent fashion. Local delivery of Bifidobacterium potently stimulates STING signaling and increases cross-priming of dendritic cells after anti-CD47 treatment. Our study identifies the mechanism by which gut microbiota preferentially colonize in tumor sites and facilitate immunotherapy via STING signaling. Rockefeller University Press 2020-03-06 /pmc/articles/PMC7201921/ /pubmed/32142585 http://dx.doi.org/10.1084/jem.20192282 Text en © 2020 Shi et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Brief Definitive Report
Shi, Yaoyao
Zheng, Wenxin
Yang, Kaiting
Harris, Katharine G.
Ni, Kaiyuan
Xue, Lai
Lin, Wenbin
Chang, Eugene B.
Weichselbaum, Ralph R.
Fu, Yang-Xin
Intratumoral accumulation of gut microbiota facilitates CD47-based immunotherapy via STING signaling
title Intratumoral accumulation of gut microbiota facilitates CD47-based immunotherapy via STING signaling
title_full Intratumoral accumulation of gut microbiota facilitates CD47-based immunotherapy via STING signaling
title_fullStr Intratumoral accumulation of gut microbiota facilitates CD47-based immunotherapy via STING signaling
title_full_unstemmed Intratumoral accumulation of gut microbiota facilitates CD47-based immunotherapy via STING signaling
title_short Intratumoral accumulation of gut microbiota facilitates CD47-based immunotherapy via STING signaling
title_sort intratumoral accumulation of gut microbiota facilitates cd47-based immunotherapy via sting signaling
topic Brief Definitive Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201921/
https://www.ncbi.nlm.nih.gov/pubmed/32142585
http://dx.doi.org/10.1084/jem.20192282
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