In situ vaccination with laser interstitial thermal therapy augments immunotherapy in malignant gliomas

Shin, David; Melnick, Kaitlyn; Tran, David; Ghiaseddin, Ashley

doi:10.1007/s11060-020-03557-x

Cited by 15 publications

(9 citation statements)

References 62 publications

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“…This underlies the refractory nature of GBM to immunotherapy. Therefore, mechanisms that optimize the tumor microenvironment are vital in enhancing a tumor-specific immune response and improving immunotherapy success for GBM 5 …”

Section: Discussionmentioning

confidence: 99%

“…Glioblastomas demonstrate a highly immunosuppressed microenvironment characterized by a lack of T-cell infiltration, cytokine dysregulation, increased counts of T reg cells and myeloid-derived suppressor cells, and anergy of tumor-infiltrating T-cells. 5 This underlies the refractory nature of GBM to immunotherapy. Therefore, mechanisms that optimize the tumor microenvironment are vital in enhancing a tumor-specific immune response and improving immunotherapy success for GBM.…”

Section: Discussionmentioning

confidence: 99%

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

Chandar,

Bhatia,

Ingle

et al. 2023

Journal of Immunotherapy

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Chandar,

Bhatia,

Ingle

et al. 2023

Journal of Immunotherapy

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“…This may improve immune cell infiltration and promote maturation [ 11 ] or improve CNS drug delivery [ 9 , 10 ], though further studies are needed. Interestingly, it has been suggested that LITT can enhance in situ immunization in GBM and potentiate the anti-tumor effect conferred by ICI [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Prolonged response of recurrent IDH -wild-type glioblastoma to laser interstitial thermal therapy with pembrolizumab

et al. 2022

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Despite the improved understanding of the molecular and genetic heterogeneity of glioblastoma, there is still an unmet need for better therapeutics, as treatment approaches have remained unchanged in recent years. Research into the role of the immune microenvironment has generated enthusiasm for testing immunotherapy (specifically, immune checkpoint inhibitors). However, to date, trials of immunotherapy in glioblastoma have not demonstrated a survival advantage. Combination approaches aimed at optimally inducing response to immune checkpoint inhibitors with radiotherapy are currently being investigated. Herein, the authors describe their experience of the potential benefit and clinical outcomes of using combination pembrolizumab (an immune checkpoint inhibitor) and laser interstitial thermal therapy in a case series of patients with recurrent IDH-wild-type glioblastoma.

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“…Therefore, several clinical trials have been conducted to explore the combination of thermal ablation (e.g., RFA, MWA) and ICB therapies or ACT therapies to treat hepatocellular carcinoma (HCC) and glioblastoma. 325 However, due to the limited immunogenicity of TAAs and the intrinsic immunosuppressive tumor microenvironment, local hyperthermia treatment-elicited tumor-specific immune responses, even in combination with ICB immunotherapies, are mostly not robust enough to prevent tumor relapse and metastasis in most cases. 326 With deeper insights into cancer immunology and vast advances in biomaterials, accumulating preclinical and clinical evidence has revealed that the rational introduction of biocompatible biomaterials could further potentiate current thermal immunotherapy.…”

Section: Thermally Enhanced Immunotherapymentioning

confidence: 99%

“…Therefore, local hyperthermia treatments have been shown to be promising to synergize with immunotherapies (abbreviated as thermal immunotherapy) to suppress tumor growth because they could also provide a sufficient bridging time window to facilitate the priming of tumor-specific T cells. Therefore, several clinical trials have been conducted to explore the combination of thermal ablation (e.g., RFA, MWA) and ICB therapies or ACT therapies to treat hepatocellular carcinoma (HCC) and glioblastoma …”

Section: Biomaterial-assisted Rational Combination Of Local Hyperther...mentioning

confidence: 99%

Rational Design of Biomaterials to Potentiate Cancer Thermal Therapy

Zhu

Wang

et al. 2023

Chem. Rev.

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Cancer thermal therapy, also known as hyperthermia therapy, has long been exploited to eradicate mass lesions that are now defined as cancer. With the development of corresponding technologies and equipment, local hyperthermia therapies such as radiofrequency ablation, microwave ablation, and high-intensity focused ultrasound, have has been validated to effectively ablate tumors in modern clinical practice. However, they still face many shortcomings, including nonspecific damages to adjacent normal tissues and incomplete ablation particularly for large tumors, restricting their wide clinical usage. Attributed to their versatile physiochemical properties, biomaterials have been specially designed to potentiate local hyperthermia treatments according to their unique working principles. Meanwhile, biomaterial-based delivery systems are able to bridge hyperthermia therapies with other types of treatment strategies such as chemotherapy, radiotherapy and immunotherapy. Therefore, in this review, we discuss recent progress in the development of functional biomaterials to reinforce local hyperthermia by functioning as thermal sensitizers to endow more efficient tumor-localized thermal ablation and/or as delivery vehicles to synergize with other therapeutic modalities for combined cancer treatments. Thereafter, we provide a critical perspective on the further development of biomaterial-assisted local hyperthermia toward clinical applications.

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In situ vaccination with laser interstitial thermal therapy augments immunotherapy in malignant gliomas

Cited by 15 publications

References 62 publications

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

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

Prolonged response of recurrent IDH -wild-type glioblastoma to laser interstitial thermal therapy with pembrolizumab

Rational Design of Biomaterials to Potentiate Cancer Thermal Therapy

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