(AS1) Development of a Murine Laser Interstitial Thermal Therapy System and Studying the Post-ablation Immune Changes in the Tumor Microenvironment in a Preclinical Glioma Model

Introduction: Laser interstitial thermal therapy (LITT) is a minimally-invasive technique that uses a laser to selectively ablate targeted lesions and minimize collateral damage to surrounding tissue. LITT is used to treat various intracranial pathologies, including brain tumors. LITT has been demonstrated to be safe and efficacious when a near-total ablation of the lesion is achieved, and additional benefits include opening the blood-brain barrier and immune activation. The kinetics of intratumoral immune changes following LITT are poorly understood, and this study was designed to establish a murine LITT system to evaluate the effect of LITT on immune changes in the tumor microenvironment (TME) and the efficacy of LITT in combination with other therapeutic treatments.

Methods: A novel murine LITT paradigm was developed that allows for stereotactic placement of a 1064nm laser into a mouse brain with real-time thermometry recordings. This paradigm was tested in an immunocompetent mouse model with orthotopic implantation of KR158b-Luciferase glioma cells. Tumor growth in mice with and without LITT treatment was monitored with bioluminescence. Histological changes following LITT were measured with hematoxylin/eosin staining. Survival experiments were conducted on twenty male C57BL/6 mice.

Results: The median survival of LITT-treated animals was increased when compared to untreated animals (44 days versus 35 days). H&E staining of brain tissue demonstrated clear evidence of localized ablation. In vivo bioluminescence demonstrated decreased tumor size in LITT-treated animals.

Conclusion : This study demonstrated the development of a novel murine LITT system for the treatment of preclinical models of glioma that leads to increased survival of tumor-bearing mice. Histological analysis and bioluminescence confirmed the targeted laser ablation of the tumor. Experiments are currently underway to investigate the consequences of LITT ablation on immune changes in the TME. These studies will be instrumental in evaluating the use of this therapeutic approach in combination with targeted immune therapies for brain malignancies.