Murine Models of Laser Interstitial Thermal Therapy for Immuno-Oncology

Abstract

INTRODUCTION: Cytoreductive surgery is a cornerstone of management for intracranial tumors. However, such treatment may remove an important source of neoantigen. In the case of laser interstital thermal therapy (LITT), thermally-ablated tumor remans in situ, allowing for a potential anti-tumor immune response. METHODS: Brain tumor cell lines (CT-2A) were stereotactically implanted into C57BL/6 mice. A 1064 nm Nd:YAG laser (Neuroblate, Monteris Medical) was used to ablate normal brain and tumor tissue. RESULTS: To establish anatomical boundaries for our ablation, we characterized our CT-2A model on T2 MRI, selecting 10 days post-implantation for LITT based on lesion size. We simultaneously implanted a 400 μm laser fiber and thermocouple probe into the center and edge of the target volume, respectively, for simultaneous ablation and temperature monitoring. To characterize the laser's effects, we first performed a dose titration of laser power/time in normal mouse brains, finding that doses above 2 W for 30 s produced cavitary lesions with charring that resulted in death at 24 h post-LITT. We therefore selected 1 W for 60 s as a safe laser power dose in our tumor model. Ablations at this setting rapidly heated the lesion edge to a peak temperature of mean 43.79 ± 2.993 °C, sparing the surrounding brain. MRI imaging at 1, 3, and 7 days post-LITT revealed an expansile T2 hyperintense lesion, with hemmorhage and necrosis on H&E. LITT increased survival to 28 from 25.5 days (vs sham, p = 0.0172). CONCLUSIONS: Using a clinical laser system, we were able to model the essential clinicopathological effects of LITT in mice: a cytoreductive survival benefit; lesion expansion on MRI; and focal necrosis with hemorrhagic vasculature on H&E. This model allows for detailed immunological studies of LITT and use with existing brain metastasis cell lines.