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Immunomodulation of intracranial melanoma in response to blood-tumor barrier opening with focused ultrasound

Background: Focused ultrasound (FUS) activation of microbubbles (MBs) for blood-brain (BBB) and blood-tumor barrier (BTB) opening permits targeted therapeutic delivery. While the effects of FUS+MBs mediated BBB opening have been investigated for normal brain tissue, no such studies exist for intracr...

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Autores principales: Curley, Colleen T., Stevens, Aaron D., Mathew, Alexander S., Stasiak, Katarzyna, Garrison, William J., Miller, G. Wilson, Sheybani, Natasha D., Engelhard, Victor H., Bullock, Timothy N.J., Price, Richard J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392000/
https://www.ncbi.nlm.nih.gov/pubmed/32754281
http://dx.doi.org/10.7150/thno.47983
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author Curley, Colleen T.
Stevens, Aaron D.
Mathew, Alexander S.
Stasiak, Katarzyna
Garrison, William J.
Miller, G. Wilson
Sheybani, Natasha D.
Engelhard, Victor H.
Bullock, Timothy N.J.
Price, Richard J.
author_facet Curley, Colleen T.
Stevens, Aaron D.
Mathew, Alexander S.
Stasiak, Katarzyna
Garrison, William J.
Miller, G. Wilson
Sheybani, Natasha D.
Engelhard, Victor H.
Bullock, Timothy N.J.
Price, Richard J.
author_sort Curley, Colleen T.
collection PubMed
description Background: Focused ultrasound (FUS) activation of microbubbles (MBs) for blood-brain (BBB) and blood-tumor barrier (BTB) opening permits targeted therapeutic delivery. While the effects of FUS+MBs mediated BBB opening have been investigated for normal brain tissue, no such studies exist for intracranial tumors. As this technology advances into clinical immunotherapy trials, it will be crucial to understand how FUS+MBs modulates the tumor immune microenvironment. Methods and Results: Bulk RNA sequencing revealed that FUS+MBs BTB/BBB opening (1 MHz, 0.5 MPa peak-negative pressure) of intracranial B16F1cOVA tumors increases the expression of genes related to proinflammatory cytokine and chemokine signaling, pattern recognition receptor signaling, and antigen processing and presentation. Flow cytometry revealed increased maturation (i.e. CD86) of dendritic cells (DCs) in the meninges and altered antigen loading of DCs in both the tumor and meninges. For DCs in tumor draining lymph nodes, FUS+MBs had no effect on maturation and elicited only a trend towards increased presentation of tumor-derived peptide by MHC. Neither tumor endothelial cell adhesion molecule expression nor homing of activated T cells was affected by FUS+MBs. Conclusion: FUS+MBs-mediated BTB/BBB opening elicits signatures of inflammation; however, the response is mild, transient, and unlikely to elicit a systemic response independent of administration of immune adjuvants.
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spelling pubmed-73920002020-08-03 Immunomodulation of intracranial melanoma in response to blood-tumor barrier opening with focused ultrasound Curley, Colleen T. Stevens, Aaron D. Mathew, Alexander S. Stasiak, Katarzyna Garrison, William J. Miller, G. Wilson Sheybani, Natasha D. Engelhard, Victor H. Bullock, Timothy N.J. Price, Richard J. Theranostics Research Paper Background: Focused ultrasound (FUS) activation of microbubbles (MBs) for blood-brain (BBB) and blood-tumor barrier (BTB) opening permits targeted therapeutic delivery. While the effects of FUS+MBs mediated BBB opening have been investigated for normal brain tissue, no such studies exist for intracranial tumors. As this technology advances into clinical immunotherapy trials, it will be crucial to understand how FUS+MBs modulates the tumor immune microenvironment. Methods and Results: Bulk RNA sequencing revealed that FUS+MBs BTB/BBB opening (1 MHz, 0.5 MPa peak-negative pressure) of intracranial B16F1cOVA tumors increases the expression of genes related to proinflammatory cytokine and chemokine signaling, pattern recognition receptor signaling, and antigen processing and presentation. Flow cytometry revealed increased maturation (i.e. CD86) of dendritic cells (DCs) in the meninges and altered antigen loading of DCs in both the tumor and meninges. For DCs in tumor draining lymph nodes, FUS+MBs had no effect on maturation and elicited only a trend towards increased presentation of tumor-derived peptide by MHC. Neither tumor endothelial cell adhesion molecule expression nor homing of activated T cells was affected by FUS+MBs. Conclusion: FUS+MBs-mediated BTB/BBB opening elicits signatures of inflammation; however, the response is mild, transient, and unlikely to elicit a systemic response independent of administration of immune adjuvants. Ivyspring International Publisher 2020-07-11 /pmc/articles/PMC7392000/ /pubmed/32754281 http://dx.doi.org/10.7150/thno.47983 Text en © The author(s) This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Curley, Colleen T.
Stevens, Aaron D.
Mathew, Alexander S.
Stasiak, Katarzyna
Garrison, William J.
Miller, G. Wilson
Sheybani, Natasha D.
Engelhard, Victor H.
Bullock, Timothy N.J.
Price, Richard J.
Immunomodulation of intracranial melanoma in response to blood-tumor barrier opening with focused ultrasound
title Immunomodulation of intracranial melanoma in response to blood-tumor barrier opening with focused ultrasound
title_full Immunomodulation of intracranial melanoma in response to blood-tumor barrier opening with focused ultrasound
title_fullStr Immunomodulation of intracranial melanoma in response to blood-tumor barrier opening with focused ultrasound
title_full_unstemmed Immunomodulation of intracranial melanoma in response to blood-tumor barrier opening with focused ultrasound
title_short Immunomodulation of intracranial melanoma in response to blood-tumor barrier opening with focused ultrasound
title_sort immunomodulation of intracranial melanoma in response to blood-tumor barrier opening with focused ultrasound
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392000/
https://www.ncbi.nlm.nih.gov/pubmed/32754281
http://dx.doi.org/10.7150/thno.47983
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