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Neurosurgeon Forum

Tumor

Infiltration of Microglia and Macrophages post-Laser Interstitial Thermal Therapy in a Preclinical Murine Glioblastoma Model

Friday, May 3, 2024
1:35 PM – 1:39 PM CT
Location:  S401ab
Disclosure(s):
Prazwal Athukuri, BS: No financial relationships to disclose
Introduction: The current standard of treatment for glioblastoma (GBM) is maximal surgical resection followed by chemotherapy and radiotherapy. Laser interstitial thermal therapy (LITT) is a treatment modality that uses thermal energy to ablate tissue and is currently being studied for its application in glioblastoma (GBM). LITT is useful to ablate tumors not appropriate for conventional surgical resection. There is a paucity of pre-clinical models of LITT to study the immune microenvironment of thermal ablation.

Methods: To simulate the poorly-circumscribed nature of glioblastomas, we developed a preclinical murine model using tumor cells overexpressing PDGFB and STAT3. We treated tumor-bearing mice with LITT or sham (laser fiber implanted but not activated). Hematoxylin and eosin (H&E), immunohistochemistry (IHC), and immunofluorescence (IF) staining were used to characterize the immune microenvironment 3, 7, 14, and 21 days after treatment.

Results: IHC staining with IBA1 3, 7, 14, and 21 days after treatment was done to evaluate for microglial activation. The LITT exhibited significant IBA1 staining in the margin of the resection cavity in comparison to the sham treatment. IF staining with IBA1 and CD68 3 and 7 days after treatment was done to evaluate for microglial activation and macrophage infiltration. Quantification of IBA1 and CD68 showed a significant increase in their expression in LITT treated mice in comparison to sham treated mice.

Conclusion : Microglial activation and macrophage infiltration induced by LITT may enhance the accessibility of immunotherapies, such as immune checkpoint inhibitors, to prevent tumor recurrence. Future studies will focus on evaluating the infiltration of T cells, NK cells, and antigen-presenting cells and evaluating the treatment efficacy of immunotherapies in conjunction with LITT through survival studies.