Modulating the glioma microenvironment with laser interstitial thermal therapy: mechanisms and therapeutic...

Glioblastoma (GBM) remains one of the most deadly brain tumors through its invasiveness, rapid growth, its immunosuppressive microenvironment, and limited treatment options. Laser interstitial thermal therapy (LITT) is an MR-guided, minimally invasive ablation technique increasingly used in GBM management. This narrative review examines how LITT modulates the glioma microenvironment and explores its therapeutic implications. We cover both preclinical and clinical studies and synthesize the effects of LITT on immune activation, blood-brain barrier (BBB) permeability, and thermal dynamics in gliomas. LITT generates three spatially distinct thermal zones, promoting damage-associated molecular pattern (DAMP) release, immune cell activation, and transient BBB disruption. These changes may help convert immunologically "cold" gliomas into "hot" tumors and enhance the delivery of chemotherapy, immunotherapy, and viral or gene-based therapies. Technical limitations, such as the heat sink effect near vascular structures, are increasingly addressed through innovations like dual-fiber systems and advanced thermal modeling. LITT is emerging as much more than a cytoreductive tool for unresectable glioma; it may provide a platform for immune modulation and therapeutic enhancement in glioma care. Potential benefits of LITT's interaction with the microenvironment and the BBB include: (1) recruitment and mobilization of the immune system to better target cancerous cells; (2) improved penetration of existing therapies; (3) which enables a lower effective dose for previously barred-drugs, reducing peripheral adverse effects; (4) improved potential for peripheral liquid biopsy. Optimizing treatment timing, patient selection, and combination protocols will be essential to fully harness LITT's biological effects and improve clinical outcomes.