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Nanoscale metal-organic frameworks enhance radiotherapy to potentiate checkpoint blockade immunotherapy

Checkpoint blockade immunotherapy enhances systemic antitumor immune response by targeting T cell inhibitory pathways; however, inadequate T cell infiltration has limited its anticancer efficacy. Radiotherapy (RT) has local immunomodulatory effects that can alter the microenvironment of irradiated t...

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Autores principales: Ni, Kaiyuan, Lan, Guangxu, Chan, Christina, Quigley, Bryan, Lu, Kuangda, Aung, Theint, Guo, Nining, La Riviere, Patrick, Weichselbaum, Ralph R., Lin, Wenbin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6003951/
https://www.ncbi.nlm.nih.gov/pubmed/29907739
http://dx.doi.org/10.1038/s41467-018-04703-w
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author Ni, Kaiyuan
Lan, Guangxu
Chan, Christina
Quigley, Bryan
Lu, Kuangda
Aung, Theint
Guo, Nining
La Riviere, Patrick
Weichselbaum, Ralph R.
Lin, Wenbin
author_facet Ni, Kaiyuan
Lan, Guangxu
Chan, Christina
Quigley, Bryan
Lu, Kuangda
Aung, Theint
Guo, Nining
La Riviere, Patrick
Weichselbaum, Ralph R.
Lin, Wenbin
author_sort Ni, Kaiyuan
collection PubMed
description Checkpoint blockade immunotherapy enhances systemic antitumor immune response by targeting T cell inhibitory pathways; however, inadequate T cell infiltration has limited its anticancer efficacy. Radiotherapy (RT) has local immunomodulatory effects that can alter the microenvironment of irradiated tumors to synergize with immune checkpoint blockade. However, even with high doses of radiation, RT has rarely elicited systemic immune responses. Herein, we report the design of two porous Hf-based nanoscale metal-organic frameworks (nMOFs) as highly effective radioenhancers that significantly outperform HfO(2), a clinically investigated radioenhancer in vitro and in vivo. Importantly, the combination of nMOF-mediated low-dose RT with an anti-programmed death-ligand 1 antibody effectively extends the local therapeutic effects of RT to distant tumors via abscopal effects. Our work establishes the feasibility of combining nMOF-mediated RT with immune checkpoint blockade to elicit systemic antitumor immunity in non-T cell-inflamed tumor phenotypes without normal tissue toxicity, promising to broaden the application of checkpoint blockade immunotherapy.
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spelling pubmed-60039512018-06-18 Nanoscale metal-organic frameworks enhance radiotherapy to potentiate checkpoint blockade immunotherapy Ni, Kaiyuan Lan, Guangxu Chan, Christina Quigley, Bryan Lu, Kuangda Aung, Theint Guo, Nining La Riviere, Patrick Weichselbaum, Ralph R. Lin, Wenbin Nat Commun Article Checkpoint blockade immunotherapy enhances systemic antitumor immune response by targeting T cell inhibitory pathways; however, inadequate T cell infiltration has limited its anticancer efficacy. Radiotherapy (RT) has local immunomodulatory effects that can alter the microenvironment of irradiated tumors to synergize with immune checkpoint blockade. However, even with high doses of radiation, RT has rarely elicited systemic immune responses. Herein, we report the design of two porous Hf-based nanoscale metal-organic frameworks (nMOFs) as highly effective radioenhancers that significantly outperform HfO(2), a clinically investigated radioenhancer in vitro and in vivo. Importantly, the combination of nMOF-mediated low-dose RT with an anti-programmed death-ligand 1 antibody effectively extends the local therapeutic effects of RT to distant tumors via abscopal effects. Our work establishes the feasibility of combining nMOF-mediated RT with immune checkpoint blockade to elicit systemic antitumor immunity in non-T cell-inflamed tumor phenotypes without normal tissue toxicity, promising to broaden the application of checkpoint blockade immunotherapy. Nature Publishing Group UK 2018-06-15 /pmc/articles/PMC6003951/ /pubmed/29907739 http://dx.doi.org/10.1038/s41467-018-04703-w Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Ni, Kaiyuan
Lan, Guangxu
Chan, Christina
Quigley, Bryan
Lu, Kuangda
Aung, Theint
Guo, Nining
La Riviere, Patrick
Weichselbaum, Ralph R.
Lin, Wenbin
Nanoscale metal-organic frameworks enhance radiotherapy to potentiate checkpoint blockade immunotherapy
title Nanoscale metal-organic frameworks enhance radiotherapy to potentiate checkpoint blockade immunotherapy
title_full Nanoscale metal-organic frameworks enhance radiotherapy to potentiate checkpoint blockade immunotherapy
title_fullStr Nanoscale metal-organic frameworks enhance radiotherapy to potentiate checkpoint blockade immunotherapy
title_full_unstemmed Nanoscale metal-organic frameworks enhance radiotherapy to potentiate checkpoint blockade immunotherapy
title_short Nanoscale metal-organic frameworks enhance radiotherapy to potentiate checkpoint blockade immunotherapy
title_sort nanoscale metal-organic frameworks enhance radiotherapy to potentiate checkpoint blockade immunotherapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6003951/
https://www.ncbi.nlm.nih.gov/pubmed/29907739
http://dx.doi.org/10.1038/s41467-018-04703-w
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