Transient Lymphatic Remodeling Follows Sub-Ablative High-Frequency Irreversible Electroporation Therapy in a 4T1 Murine Model

• DOI: 10.1007/s10439-024-03674-y
• Publication Date: 2025-02-25T16:12:52Z
• Authors: Savieay Esparza; Edward Jacobs; Jennifer H. Hammel; Sharon K. Michelh...; Nastaran Alinezha...; Margaret Nagai-Si...; Khan Mohammad Imran; Rafael V. Davalos; Irving C. Allen; Scott S. Verbridge; Jennifer M. Munson
• Keywords: Lymphatic vessel; Lymphatic Endothelium; CCL21

Abstract High-frequency irreversible electroporation (H-FIRE) is a minimally invasive local ablation therapy known to activate the adaptive immune system and reprogram tumor microenvironment. Its predecessor, (IRE), transiently increases microvascular density cell infiltration within surviving non-ablated non-necrotic region, also as viable region. However, impact of pulse electric field therapies on lymphatic vessels, crucial for T-cell fate maturation, remains unclear. This study investigates how sub-ablative H-FIRE (SA-HFIRE) affects blood remodeling in 4T1 mammary mouse model. We conducted temporal spatial analysis evaluate vascular changes tumor, peritumoral fat pad, tumor-draining lymph node post-treatment. Histological examination showed transient increase vessel Day 1 post-treatment, followed by spike region 3 increased peripheral minimal days following treatment. Gene expression indicated elevated levels CCL21 CXCL2 while VEGFA VEGFC did not appear contribute remodeling. Likewise, protein content axillary nodes correlated with gene data from These findings suggest dynamic shift structures post-SA-HFIRE, potentially enhancing response through CCL21-mediated homing subsequent Future work will assess transport function microvasculature inform experiments aimed at application adjuvant during scenarios partial ablation.