Laser ablation: Heating up the anti-tumor response in the intracranial compartment

Abstract

Immunotherapies, such as immune checkpoint inhibition (ICI), have had limited success in treating intracranial malignancies. These failures are due partly to the restrictive blood-brain-barrier (BBB), the profound tumor-dependent induction of local and systemic immunosuppression, and immune evasion exhibited by these tumors. Therefore, novel approaches must be explored that aim to overcome these stringent barriers. LITT is an emerging treatment for brain tumors that utilizes thermal ablation to kill tumor cells. LITT provides an additional therapeutic benefit by synergizing with ICI and systemic chemotherapies to strengthen the anti-tumor immune response. This synergistic relationship involves transient disruption of the BBB and local augmentation of immune function, culminating in increased CNS drug penetrance and improved anti-tumor immunity. In this review, we will provide an overview of the challenges facing immunotherapy for brain tumors, and discuss how LITT may synergize with the endogenous anti-tumor response to improve the efficacy of ICI.

Keywords: Anti-tumor immunity; Blood brain barrier; Brain metastases; Checkpoint blockade; Checkpoint inhibition; Glioblastoma; Glioma; Hyperthermia; Immunotherapy; Intracranial tumors; LITT laser interstitial thermal therapy.