42 Laser Interstitial Thermal Therapy (Litt) Mouse Model Unveils Cellular Responses in Tumor Brain

INTRODUCTION Glioblastoma accounts for 48%-60% of adult high-grade primary brain tumors and has a 5-year net survival of only 4.8%. LITT is a minimally-invasive hyperthermic ablation method indicated for inoperable brain tumors. We have established a preclinical murine model of LITT in glioblastoma to study the cellular effects and explore novel drug treatments in the future. METHODS Syngeneic glioma cell-line CT2A is orthotopically implanted into C57BL/6 mice using a stereotactic frame. Tumor burden is monitored using T2-weighted MRI, with post-operative scans for treatment confirmation. LITT using a custom 1064nm fibreoptic laser or a surgical sham with conventional tissue damage are performed. Brains, cervical lymph nodes, and blood plasma are collected at relevant timepoints, providing both local and systemic views of the inflammatory/immune processes in response to LITT. RESULTS LITT conditions were optimized to ensure well-tolerated and effective ablation of tumor tissue. Multiplexed immunofluorescence highlighted spatiotemporal changes to resident and immune cell populations including activation of resident microglia and phagocyte recruitment.Astrocytes at the LITT site differed in marker expression suggesting distinct subpopulations. Single-cell spatial transcriptomics also identified well-defined gene clusters indicative of distinct cell populations in LITT brains. Analysis of plasma cytokines will determine if brain LITT can evoke systemic cytokine changes which may be relevant in underpinning immunomodulatory mechanisms. CONCLUSION Successful establishment of this LITT murine model provides a valuable platform for investigating LITT effects on the tumor, tumor- microenvironment, and the systemic cytokine milieu. This unique preclinical model empowers the discovery of combined LITT-drug treatments for improved therapeutic efficacy.