An orthotopically allografted mouse GL26 glioma model (Ccr2RFP/wt–Cx3cr1GFP/wt) was used to evaluate the effect of transient, focal opening of the blood–brain barrier
(BBB) on the composition of tumor-associated macrophages and microglia (TAMs). BBB
opening was induced by magnetic resonance imaging (MRI)–guided focused ultrasound
(MRgFUS) combined with microbubbles. CX3CR1-GFP cells and CCR2-RFP cells in brain
tumors were quantified in microscopic images. Tumors in animals treated with a single
session of MRgFUS did not exhibit significant changes in cell numbers when compared
with tumors in animals not receiving FUS. However, tumors that received two or three
sessions of MRgFUS had significantly increased amounts of both CX3CR1-GFP and CCR2-RFP
cells. The effect of MRgFUS on immune cell composition was also characterized and
quantified using flow cytometry. Glioma implantation resulted in increased amounts
of lymphocytes, monocytes and neutrophils in the brain parenchyma. Tumors administered
MRgFUS exhibited increased numbers of monocytes and monocyte-derived TAMs. In addition,
MRgFUS-treated tumors exhibited more CD80+ cells in monocytes and microglia. In summary,
transient, focal opening of the BBB using MRgFUS combined with microbubbles can activate
the homing and differentiation of monocytes and induce a shift toward a more pro-inflammatory
status of the immune environment in glioblastoma.
Keywords
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Article info
Publication history
Published online: January 28, 2023
Accepted:
December 10,
2022
Received in revised form:
November 11,
2022
Received:
August 31,
2022
Identification
Copyright
© 2022 World Federation for Ultrasound in Medicine & Biology. All rights reserved.
