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Theranostics 2020; 10(19):8821-8833. doi:10.7150/thno.47983 This issue Cite

Research Paper

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

Colleen T. Curley1, Aaron D. Stevens2, Alexander S. Mathew1, Katarzyna Stasiak3, William J. Garrison1, G. Wilson Miller1,4, Natasha D. Sheybani1✉, Victor H. Engelhard3, Timothy N.J. Bullock2✉, Richard J. Price1,4✉

1. Department of Biomedical Engineering, University of Virginia, Charlottesville, VA
2. Department of Pathology, University of Virginia, Charlottesville, VA
3. Carter Immunology Center and Department of Microbiology, Immunology, and Cancer Biology, Charlottesville, VA
4. Department of Radiology & Medical Imaging, University of Virginia, Charlottesville, VA

✉ Corresponding authors: Richard J. Price, Ph.D., Department of Biomedical Engineering, Box 800759, Health System, University of Virginia, Charlottesville, VA 22908, USA. Telephone: (434) 924-0020; Email: rpriceedu. Timothy N.J. Bullock, Ph. More

Citation:
Curley CT, Stevens AD, Mathew AS, Stasiak K, Garrison WJ, Miller GW, Sheybani ND, Engelhard VH, Bullock TNJ, Price RJ. Immunomodulation of intracranial melanoma in response to blood-tumor barrier opening with focused ultrasound. Theranostics 2020; 10(19):8821-8833. doi:10.7150/thno.47983. https://www.thno.org/v10p8821.htm
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Abstract

Graphic abstract

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.

Keywords: focused ultrasound, blood-tumor barrier, inflammation, immune cells, RNA sequencing

Citation styles

APA
Curley, C.T., Stevens, A.D., Mathew, A.S., Stasiak, K., Garrison, W.J., Miller, G.W., Sheybani, N.D., Engelhard, V.H., Bullock, T.N.J., Price, R.J. (2020). Immunomodulation of intracranial melanoma in response to blood-tumor barrier opening with focused ultrasound. Theranostics, 10(19), 8821-8833. https://doi.org/10.7150/thno.47983.

ACS
Curley, C.T.; Stevens, A.D.; Mathew, A.S.; Stasiak, K.; Garrison, W.J.; Miller, G.W.; Sheybani, N.D.; Engelhard, V.H.; Bullock, T.N.J.; Price, R.J. Immunomodulation of intracranial melanoma in response to blood-tumor barrier opening with focused ultrasound. Theranostics 2020, 10 (19), 8821-8833. DOI: 10.7150/thno.47983.

NLM
Curley CT, Stevens AD, Mathew AS, Stasiak K, Garrison WJ, Miller GW, Sheybani ND, Engelhard VH, Bullock TNJ, Price RJ. Immunomodulation of intracranial melanoma in response to blood-tumor barrier opening with focused ultrasound. Theranostics 2020; 10(19):8821-8833. doi:10.7150/thno.47983. https://www.thno.org/v10p8821.htm

CSE
Curley CT, Stevens AD, Mathew AS, Stasiak K, Garrison WJ, Miller GW, Sheybani ND, Engelhard VH, Bullock TNJ, Price RJ. 2020. Immunomodulation of intracranial melanoma in response to blood-tumor barrier opening with focused ultrasound. Theranostics. 10(19):8821-8833.

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