TY - JOUR
T1 - Molecular Identity Changes of Tumor-Associated Macrophages and Microglia After Magnetic Resonance Imaging–Guided Focused Ultrasound–Induced Blood–Brain Barrier Opening in a Mouse Glioblastoma Model
AU - Zhang, Yanrong
AU - Wang, Jing
AU - Ghobadi, Sara Natasha
AU - Zhou, Haiyan
AU - Huang, Ai
AU - Gerosa, Marco
AU - Hou, Qingyi
AU - Keunen, Olivier
AU - Golebiewska, Anna
AU - Habte, Frezghi G.
AU - Grant, Gerald A.
AU - Paulmurugan, Ramasamy
AU - Lee, Kevin S.
AU - Wintermark, Max
N1 - Funding Information:
This work was supported by National Institutes of Health Grants R01 CA217953-01 and R01 NS102194 .
Publisher Copyright:
© 2022 World Federation for Ultrasound in Medicine & Biology
PY - 2023/5
Y1 - 2023/5
N2 - 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.
AB - 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.
KW - Focused ultrasound
KW - Glioblastoma
KW - Magnetic resonance imaging–guided focused ultrasound
KW - Microbubbles
KW - Microglia and macrophage activation
KW - Sterile inflammation
KW - Tumor-associated macrophages and microglia
UR - http://www.scopus.com/inward/record.url?scp=85147121113&partnerID=8YFLogxK
UR - https://pubmed.ncbi.nlm.nih.gov/36717283
U2 - 10.1016/j.ultrasmedbio.2022.12.006
DO - 10.1016/j.ultrasmedbio.2022.12.006
M3 - Article
C2 - 36717283
AN - SCOPUS:85147121113
SN - 0301-5629
VL - 49
SP - 1082
EP - 1090
JO - Ultrasound in Medicine and Biology
JF - Ultrasound in Medicine and Biology
IS - 5
ER -