TMOD-18. Tumor Ablation and Immune Microenvironment Modulation Following Laser Interstitial Thermal Therapy in a Murine Glioblastoma Model

Abstract TITLE Tumor Ablation and Immune Microenvironment Modulation Following Laser Interstitial Thermal Therapy in a Murine Glioblastoma Model AUTHORS Ashley Puentes, Prazwal Athukuri, MD, Karina V. Moreno, Yuhui Yang, MS, Malcolm F. MacDonald, Anantha Marisetty, PhD, Sungho Lee, MD, Khatri Latha, PhD, David Needham, PhD, DSc, Ganesh Rao, MD ABSTRACT Glioblastoma (GBM) is an aggressive brain tumor with limited treatment options, particularly when surgical resection is not feasible. Laser interstitial thermal therapy (LITT) is a minimally invasive technique that delivers focused thermal ablation to tumor tissue. We evaluated the efficacy and immunological effects of LITT using a murine GBM model. C57BL/6 mice were orthotopically implanted with GL261-luciferase cells in the right frontal cortex. Five days post-implantation, mice underwent LITT or Sham treatment (laser fiber placement without activation). LITT was administered using a 1064-nm laser probe with thermal regulation maintained at 46°C. Tumor progression was monitored via bioluminescent imaging (BLI), revealing significant signal reductions at days 3, 7, and 14 in LITT-treated mice, whereas Sham controls exhibited progressive tumor growth. H&E staining confirmed well-demarcated ablation zones with central necrosis. Immunofluorescence analyses showed increased activation of Iba1+ microglia/macrophages and infiltration of CD3+, CD4+, and CD8+ T cells following LITT, especially at early time points. LITT also disrupted the blood-brain barrier, as evidenced by Evans blue dye extravasation. Survival analysis demonstrated a significant benefit for LITT-treated mice compared to Sham controls (p = 0.0287). These findings establish LITT as an effective approach for reducing tumor burden and promoting immune cell infiltration in a preclinical GBM model. The observed microglial activation and T cell recruitment suggest that LITT may enhance responsiveness to immunotherapy, particularly checkpoint inhibitors. This combinatorial strategy may offer new therapeutic opportunities for GBM, especially in cases where surgical resection is not feasible.