High-frequency irreversible electroporation improves survival and immune cell infiltration in rodents with malignant gliomas

被引:20
作者
Campelo, Sabrina N. [1 ,2 ]
Lorenzo, Melvin F. [1 ,2 ]
Partridge, Brittanie [3 ]
Alinezhadbalalami, Nastaran [1 ,2 ]
Kani, Yukitaka [3 ]
Garcia, Josefa [3 ]
Saunier, Sofie [1 ,2 ]
Thomas, Sean C. [2 ]
Hinckley, Jonathan [3 ]
Verbridge, Scott S. [2 ]
Davalos, Rafael V. [1 ,2 ]
Rossmeisl Jr, John H. H. [3 ]
机构
[1] Virginia Tech, Bioelectromech Syst Lab, Blacksburg, VA USA
[2] Virginia Tech Wake Forest Univ, Sch Biomed Engn & Sci, Blacksburg, VA USA
[3] Virginia Tech, Dept Small Anim Clin Sci, Blacksburg, VA 24061 USA
基金
美国国家卫生研究院;
关键词
glioblastoma; intracranial; electroporation; blood-brain barrier disruption; immune response; numerical modeling; pulsed electric field (PEF); TUMOR-TREATING FIELDS; INTERSTITIAL THERMAL THERAPY; BLOOD-BRAIN-BARRIER; GLIOBLASTOMA; DISRUPTION;
D O I
10.3389/fonc.2023.1171278
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BackgroundIrreversible electroporation (IRE) has been previously investigated in preclinical trials as a treatment for intracranial malignancies. Here, we investigate next generation high-frequency irreversible electroporation (H-FIRE), as both a monotherapy and a combinatorial therapy, for the treatment of malignant gliomas. MethodsHydrogel tissue scaffolds and numerical modeling were used to inform in-vivo H-FIRE pulsing parameters for our orthotopic tumor-bearing glioma model. Fischer rats were separated into five treatment cohorts including high-dose H-FIRE (1750V/cm), low-dose H-FIRE (600V/cm), combinatorial high-dose H-FIRE + liposomal doxorubicin, low-dose H-FIRE + liposomal doxorubicin, and standalone liposomal doxorubicin groups. Cohorts were compared against a standalone tumor-bearing sham group which received no therapeutic intervention. To further enhance the translational value of our work, we characterize the local and systemic immune responses to intracranial H-FIRE at the study timepoint. ResultsThe median survival for each cohort are as follows: 31 days (high-dose H-FIRE), 38 days (low-dose H-FIRE), 37.5 days (high-dose H-FIRE + liposomal doxorubicin), 27 days (low-dose H-FIRE + liposomal doxorubicin), 20 days (liposomal doxorubicin), and 26 days (sham). A statistically greater overall survival fraction was noted in the high-dose H-FIRE + liposomal doxorubicin (50%, p = 0.044), high-dose H-FIRE (28.6%, p = 0.034), and the low-dose H-FIRE (20%, p = 0.0214) compared to the sham control (0%). Compared to sham controls, brain sections of rats treated with H-FIRE demonstrated significant increases in IHC scores for CD3+ T-cells (p = 0.0014), CD79a+ B-cells (p = 0.01), IBA-1+ dendritic cells/microglia (p = 0.04), CD8+ cytotoxic T-cells (p = 0.0004), and CD86+ M1 macrophages (p = 0.01). ConclusionsH-FIRE may be used as both a monotherapy and a combinatorial therapy to improve survival in the treatment of malignant gliomas while also promoting the presence of infiltrative immune cells.
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页数:18
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