High-frequency irreversible electroporation improves survival and immune cell infiltration in rodents with malignant gliomas.
High-frequency irreversible electroporation improves survival and immune cell infiltration in rodents with malignant gliomas.
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DOI：
10.3389/fonc.2023.1171278
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发表时间：
2023
影响因子：
4.7
通讯作者：
Rossmeisl Jr, John H. H.
中科院分区：
文献类型：
--
作者：
Campelo, Sabrina N.;Lorenzo, Melvin F.;Partridge, Brittanie;Alinezhadbalalami, Nastaran;Kani, Yukitaka;Garcia, Josefa;Saunier, Sofie;Thomas, Sean C.;Hinckley, Jonathan;Verbridge, Scott S.;Davalos, Rafael V.;Rossmeisl Jr, John H. H.
关键词：
不可逆电穿孔（IRE）此前已在临床前试验中作为治疗颅内恶性肿瘤的方法进行了研究。在这里，我们研究下一代高频不可逆电穿孔（H-FIRE），作为单一疗法和组合疗法，用于治疗恶性胶质瘤。水凝胶组织支架和数值建模用于告知我们的原位荷瘤胶质瘤模型的体内H-FIRE脉冲参数。将Fischer大鼠分成五个治疗组，包括高剂量H-FIRE（1750 V/cm）、低剂量H-FIRE（600 V/cm）、组合高剂量H-FIRE +脂质体多柔比星、低剂量H-FIRE +脂质体多柔比星和单独脂质体多柔比星组。将队列与未接受治疗干预的独立荷瘤假手术组进行比较。为了进一步提高我们工作的转化价值，我们在研究时间点描述了对颅内H-FIRE的局部和全身免疫应答。每个队列的中位生存期如下：31天（高剂量H-FIRE）、38天（低剂量H-FIRE）、37.5天（高剂量H-FIRE +脂质体多柔比星）、27天（低剂量H-FIRE +脂质体多柔比星）、20天（脂质体多柔比星）和26天（假手术）。与假手术对照组（0%）相比，在高剂量H-FIRE +脂质体阿霉素（50%，p = 0.044）、高剂量H-FIRE（28.6%，p = 0.034）和低剂量H-FIRE（20%，p = 0.0214）中观察到统计学上更大的总生存分数。与假手术对照组相比，用H-FIRE处理的大鼠的脑切片显示CD 3 + T细胞（p = 0.0014）、CD 79 a + B细胞（p = 0.01）、IBA-1+树突细胞/小胶质细胞（p = 0.04）、CD 8+细胞毒性T细胞（p = 0.0004）和CD 86 + M1巨噬细胞（p = 0.01）的IHC评分显著增加。H-FIRE可用作单一疗法和组合疗法，以提高恶性胶质瘤治疗中的存活率，同时还促进浸润性免疫细胞的存在。
Irreversible 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. Hydrogel 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. The 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). H-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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影响因子：
5.4
作者：
Gernert M;Feja M
通讯作者：
Feja M
影响因子：
3.9
作者：
Arena CB;Sano MB;Rossmeisl JH Jr;Caldwell JL;Garcia PA;Rylander MN;Davalos RV
通讯作者：
Davalos RV
影响因子：
11.1
作者：
Ringel-Scaia, Veronica M.;Beitel-White, Natalie;Allen, Irving C.
通讯作者：
Allen, Irving C.
影响因子：
2.8
作者：
Latouche EL;Arena CB;Ivey JW;Garcia PA;Pancotto TE;Pavlisko N;Verbridge SS;Davalos RV;Rossmeisl JH
通讯作者：
Rossmeisl JH
影响因子：
--
作者：
Arena, Christopher B.;Garcia, Paulo A.;Davalos, Rafael V.
通讯作者：
Davalos, Rafael V.