Laser Interstitial Thermal Therapy Induces Robust Local Immune Response for Newly Diagnosed Glioblastoma With Long-term Survival and Disease Control

Author:

Chandar Jay S.12,Bhatia Shovan1,Ingle Shreya1,Mendez Valdez Mynor J.1,Maric Dragan3,Seetharam Deepa1,Desgraves Jelisah F.1,Govindarajan Vaidya1,Daggubati Lekhaj1,Merenzon Martin1,Morell Alexis1,Luther Evan1,Saad Ali G.1,Komotar Ricardo J.1,Ivan Michael E.1,Shah Ashish H.1

Affiliation:

1. Department of Neurosurgery, University of Miami School of Medicine, Miami, FL

2. Florida International University Herbert Wertheim College of Medicine, Miami, FL

3. National Institutes of Health, National Institute of Neurological Disorders and Stroke (NINDS), Bethesda, MD

Abstract

Laser interstitial thermal therapy (LITT) is a minimally invasive neurosurgical technique used to ablate intra-axial brain tumors. The impact of LITT on the tumor microenvironment is scarcely reported. Nonablative LITT-induced hyperthermia (33–43˚C) increases intra-tumoral mutational burden and neoantigen production, promoting immunogenic cell death. To understand the local immune response post-LITT, we performed longitudinal molecular profiling in a newly diagnosed glioblastoma and conducted a systematic review of anti-tumoral immune responses after LITT. A 51-year-old male presented after a fall with progressive dizziness, ataxia, and worsening headaches with a small, frontal ring-enhancing lesion. After clinical and radiographic progression, the patient underwent stereotactic needle biopsy, confirming an IDH-WT World Health Organization Grade IV Glioblastoma, followed by LITT. The patient was subsequently started on adjuvant temozolomide, and 60 Gy fractionated radiotherapy to the post-LITT tumor volume. After 3 months, surgical debulking was conducted due to perilesional vasogenic edema and cognitive decline, with H&E staining demonstrating perivascular lymphocytic infiltration. Postoperative serial imaging over 3 years showed no evidence of tumor recurrence. The patient is currently alive 9 years after diagnosis. Multiplex immunofluorescence imaging of pre-LITT and post-LITT biopsies showed increased CD8 and activated macrophage infiltration and programmed death ligand 1 expression. This is the first depiction of the in-situ immune response to LITT and the first human clinical presentation of increased CD8 infiltration and programmed death ligand 1 expression in post-LITT tissue. Our findings point to LITT as a treatment approach with the potential for long-term delay of recurrence and improving response to immunotherapy.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Cancer Research,Pharmacology,Immunology,Immunology and Allergy

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