GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE325nnn/GSE325414/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE325414GEOGSEfalsePulsed Electric Field Ablation Reprograms Tumor Immunity and Stimulates Germinal Center Formation in Tertiary Lymphoid Structures in Patients with Non-Small Cell Lung CancerPurpose: This treat-and-resect clinical study evaluated a specialized form of pulsed electric field (PEF) ablation’s potential to modulate antitumor immunity in early-stage non-small cell lung cancer (NSCLC). Tertiary lymphoid structures (TLS) are lymphoid aggregates that recruit immune cells into the tumor microenvironment (TME) and serve as immunity-generating neighborhoods. TLS with germinal centers (GC) have strong prognostic value in most cancers and promote tumor control and responsiveness to immune-based therapies, but no commercially available therapeutics induce their formation. The Aliya System is a proprietary electrosurgical technology that delivers microsecond electrical pulses to tissue, achieving tumor clearance while maintaining stromal architecture. Patients and Methods: Treatment group patients received ablation immediately after diagnostic biopsy versus a biopsy-only control group. Herein we report on exploratory endpoints examining immune modulation in blood and tumor samples collected from patients in both groups. Results: Histopathological assessments revealed the presence of TLS with GC in resected tumors. Tissue cytokine assessments and single-cell RNA sequencing demonstrated upregulation of cytokines capable of recruiting and organizing TLS-associated lymphocytes, including CXCL13, and significant increases in GC-related immune populations, including class-switched memory B cells and plasma cells in ablated tumors versus pre-ablation biopsies. Ablation group patients had more tumors containing TLS with GC (47%) vs. control (24%). Ablation group patients exhibited enhanced systemic immunity, with increased serum HMGB1 and circulating cytotoxic T cells. Conclusions: This specialized PEF may orchestrate multiple simultaneous changes that promote a more immunologically active TME and represent a new approach for improving immunotherapeutic regimen responses in NSCLC patients.2026/06/10GSE325414GSM9602805GSM9602849GSM9602848GSM9602804GSM9602807GSM9602806GSM9602845GSM9602801GSM9602800GSM9602844GSM9602803GSM9602847GSM9602846GSM9602802GSM9602841GSM9602840GSM9602843GSM9602842GSM9602791GSM9602790GSM9602838GSM9602837GSM9602839GSM9602834GSM9602833GSM9602836GSM9602835GSM9602797GSM9602830GSM9602796GSM9602832GSM9602799GSM9602831GSM9602798GSM9602793GSM9602792GSM9602795GSM9602794GSM9602819GSM9602827GSM9602826GSM9602829GSM9602828GSM9602823GSM9602789GSM9602822GSM9602825GSM9602824GSM9602788GSM9602821GSM9602820GSM9602809GSM9602808GSM9602816GSM9602815GSM9602818GSM9602817GSM9602812GSM9602811GSM9602814GSM9602813GSM9602852GSM9602851GSM9602854GSM9602810GSM9602853GSM960285024676325414Homo sapiens