{"doi":"10.3389/fonc.2023.1171278","title":"High-frequency irreversible electroporation improves survival and immune cell infiltration in rodents with malignant gliomas","abstract":"Background: 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. Methods: 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. Results: 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). Conclusions: 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.","journal":"Frontiers in Oncology","year":2023,"id":325778,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":30,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9627,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":350008,"name":"Melvin F. Lorenzo","orcid":"0000-0002-6518-5398","position":1,"is_corresponding":false},{"id":351976,"name":"Brittanie Partridge","orcid":null,"position":2,"is_corresponding":false},{"id":777458,"name":"Nastaran Alinezhadbalalami","orcid":"0000-0003-2843-361X","position":3,"is_corresponding":false},{"id":396815,"name":"Yukitaka Kani","orcid":"0000-0002-7611-2741","position":4,"is_corresponding":false},{"id":857784,"name":"Josefa K. Garcia Mora","orcid":"0000-0001-6284-6210","position":5,"is_corresponding":false},{"id":1044675,"name":"Sofie Saunier","orcid":null,"position":6,"is_corresponding":false},{"id":1044085,"name":"Sean C. Thomas","orcid":"0009-0003-7030-1810","position":7,"is_corresponding":false},{"id":536390,"name":"Jonathan Hinckley","orcid":"0000-0001-9868-1163","position":8,"is_corresponding":false},{"id":233117,"name":"Scott S. Verbridge","orcid":"0000-0002-4074-8799","position":9,"is_corresponding":false},{"id":297447,"name":"Rafael V. Davalos","orcid":"0000-0003-1503-9509","position":10,"is_corresponding":false},{"id":279129,"name":"John H. Rossmeisl","orcid":"0000-0003-1655-7076","position":11,"is_corresponding":false},{"id":725700,"name":"Sabrina N. Campelo","orcid":"0000-0001-6570-7427","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":null,"created_at":"2026-07-19T01:08:28.266998Z","pmid":"37213298","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}