Pulsed Electric Field Ablation Reprograms Tumor Immunity and Stimulates Germinal Center Formation in Tertiary Lymphoid Structures in Patients with Non-Small Cell Lung Cancer

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.