Immune modulation resulting from MR-guided high intensity focused ultrasound in a model of murine breast cancer

Abstract High intensity focused ultrasound (HIFU) rapidly and non-invasively destroys tumor tissue. Here, we sought to assess the immunomodulatory effects of MR-guided HIFU and its combination with the innate immune agonist CpG and checkpoint inhibitor anti-PD-1. Mice with multi-focal breast cancer...

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Autores principales:	Brett Z. Fite, James Wang, Aris J. Kare, Asaf Ilovitsh, Michael Chavez, Tali Ilovitsh, Nisi Zhang, Weiyu Chen, Elise Robinson, Hua Zhang, Azadeh Kheirolomoom, Matthew T. Silvestrini, Elizabeth S. Ingham, Lisa M. Mahakian, Sarah M. Tam, Ryan R. Davis, Clifford G. Tepper, Alexander D. Borowsky, Katherine W. Ferrara
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3b05fd16d36d4a2eaa4db739670dbc41
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spelling	oai:doaj.org-article:3b05fd16d36d4a2eaa4db739670dbc412021-12-02T14:01:36ZImmune modulation resulting from MR-guided high intensity focused ultrasound in a model of murine breast cancer10.1038/s41598-020-80135-12045-2322https://doaj.org/article/3b05fd16d36d4a2eaa4db739670dbc412021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-80135-1https://doaj.org/toc/2045-2322Abstract High intensity focused ultrasound (HIFU) rapidly and non-invasively destroys tumor tissue. Here, we sought to assess the immunomodulatory effects of MR-guided HIFU and its combination with the innate immune agonist CpG and checkpoint inhibitor anti-PD-1. Mice with multi-focal breast cancer underwent ablation with a parameter set designed to achieve mechanical disruption with minimal thermal dose or a protocol in which tumor temperature reached 65 °C. Mice received either HIFU alone or were primed with the toll-like receptor 9 agonist CpG and the checkpoint modulator anti-PD-1. Both mechanical HIFU and thermal ablation induced a potent inflammatory response with increased expression of Nlrp3, Jun, Mefv, Il6 and Il1β and alterations in macrophage polarization compared to control. Furthermore, HIFU upregulated multiple innate immune receptors and immune pathways, including Nod1, Nlrp3, Aim2, Ctsb, Tlr1/2/4/7/8/9, Oas2, and RhoA. The inflammatory response was largely sterile and consistent with wound-healing. Priming with CpG attenuated Il6 and Nlrp3 expression, further upregulated expression of Nod2, Oas2, RhoA, Pycard, Tlr1/2 and Il12, and enhanced T-cell number and activation while polarizing macrophages to an anti-tumor phenotype. The tumor-specific antigen, cytokines and cell debris liberated by HIFU enhance response to innate immune agonists.Brett Z. FiteJames WangAris J. KareAsaf IlovitshMichael ChavezTali IlovitshNisi ZhangWeiyu ChenElise RobinsonHua ZhangAzadeh KheirolomoomMatthew T. SilvestriniElizabeth S. InghamLisa M. MahakianSarah M. TamRyan R. DavisClifford G. TepperAlexander D. BorowskyKatherine W. FerraraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Brett Z. Fite James Wang Aris J. Kare Asaf Ilovitsh Michael Chavez Tali Ilovitsh Nisi Zhang Weiyu Chen Elise Robinson Hua Zhang Azadeh Kheirolomoom Matthew T. Silvestrini Elizabeth S. Ingham Lisa M. Mahakian Sarah M. Tam Ryan R. Davis Clifford G. Tepper Alexander D. Borowsky Katherine W. Ferrara Immune modulation resulting from MR-guided high intensity focused ultrasound in a model of murine breast cancer
description	Abstract High intensity focused ultrasound (HIFU) rapidly and non-invasively destroys tumor tissue. Here, we sought to assess the immunomodulatory effects of MR-guided HIFU and its combination with the innate immune agonist CpG and checkpoint inhibitor anti-PD-1. Mice with multi-focal breast cancer underwent ablation with a parameter set designed to achieve mechanical disruption with minimal thermal dose or a protocol in which tumor temperature reached 65 °C. Mice received either HIFU alone or were primed with the toll-like receptor 9 agonist CpG and the checkpoint modulator anti-PD-1. Both mechanical HIFU and thermal ablation induced a potent inflammatory response with increased expression of Nlrp3, Jun, Mefv, Il6 and Il1β and alterations in macrophage polarization compared to control. Furthermore, HIFU upregulated multiple innate immune receptors and immune pathways, including Nod1, Nlrp3, Aim2, Ctsb, Tlr1/2/4/7/8/9, Oas2, and RhoA. The inflammatory response was largely sterile and consistent with wound-healing. Priming with CpG attenuated Il6 and Nlrp3 expression, further upregulated expression of Nod2, Oas2, RhoA, Pycard, Tlr1/2 and Il12, and enhanced T-cell number and activation while polarizing macrophages to an anti-tumor phenotype. The tumor-specific antigen, cytokines and cell debris liberated by HIFU enhance response to innate immune agonists.
format	article
author	Brett Z. Fite James Wang Aris J. Kare Asaf Ilovitsh Michael Chavez Tali Ilovitsh Nisi Zhang Weiyu Chen Elise Robinson Hua Zhang Azadeh Kheirolomoom Matthew T. Silvestrini Elizabeth S. Ingham Lisa M. Mahakian Sarah M. Tam Ryan R. Davis Clifford G. Tepper Alexander D. Borowsky Katherine W. Ferrara
author_facet	Brett Z. Fite James Wang Aris J. Kare Asaf Ilovitsh Michael Chavez Tali Ilovitsh Nisi Zhang Weiyu Chen Elise Robinson Hua Zhang Azadeh Kheirolomoom Matthew T. Silvestrini Elizabeth S. Ingham Lisa M. Mahakian Sarah M. Tam Ryan R. Davis Clifford G. Tepper Alexander D. Borowsky Katherine W. Ferrara
author_sort	Brett Z. Fite
title	Immune modulation resulting from MR-guided high intensity focused ultrasound in a model of murine breast cancer
title_short	Immune modulation resulting from MR-guided high intensity focused ultrasound in a model of murine breast cancer
title_full	Immune modulation resulting from MR-guided high intensity focused ultrasound in a model of murine breast cancer
title_fullStr	Immune modulation resulting from MR-guided high intensity focused ultrasound in a model of murine breast cancer
title_full_unstemmed	Immune modulation resulting from MR-guided high intensity focused ultrasound in a model of murine breast cancer
title_sort	immune modulation resulting from mr-guided high intensity focused ultrasound in a model of murine breast cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/3b05fd16d36d4a2eaa4db739670dbc41
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Immune modulation resulting from MR-guided high intensity focused ultrasound in a model of murine breast cancer

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