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

PURPOSE: 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

Histopathologic 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 and plasma cells in ablated tumors versus preablation biopsies. Ablation group patients had more tumors containing TLS with GC (47%) versus control (24%). Ablation group patients exhibited enhanced systemic immunity, with increased serum high mobility group box 1 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 patients with NSCLC.