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

Lerner, Emily; Edwards, Ryan; Wilkinson, Daniel; Fecci, Peter E.

doi:10.1016/j.addr.2022.114311

Cited by 29 publications

(27 citation statements)

References 157 publications

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“…Besides, Zn‐LDH causes the significant overexpression of ISG56 and IFNB1 (hallmarks of the activation of cGas‐STING signaling pathway for inducing antitumor CTL response [ 8a ] ) by 4.1‐ and 2.0‐folds, respectively (Figure 3i). Meanwhile, the tumor antigens released during ICD [ 34 ] can be adsorbed onto the positively charged Zn‐LDH to form the in situ vaccine for the efficient pickup by DCs. In a B16F10‐OVA mouse model, DC and macrophages effectively present MHC‐I/SIINFKEL (T cell epitope of OVA) in tdLNs of mice treated with Zn‐LDH, which is significantly higher than those treated with LDH and ZnCl 2 (Figure 3j,k; Figure S20, Supporting Information).…”

Section: Resultsmentioning

confidence: 99%

A Peritumorally Injected Immunomodulating Adjuvant Elicits Robust and Safe Metalloimmunotherapy against Solid Tumors

Zhang

Zhao

et al. 2022

Advanced Materials

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Clinical immunotherapy of solid tumors elicits durable responses only in a minority of patients, largely due to the highly immunosuppressive tumor microenvironment (TME). Although rational combinations of vaccine adjuvants with inflammatory cytokines or immune agonists that relieve immunosuppression represent an appealing therapeutic strategy against solid tumors, there are unavoidable nonspecific toxicities due to the pleiotropy of cytokines and undesired activation of off‐target cells. Herein, a Zn2+ doped layered double hydroxide (Zn‐LDH) based immunomodulating adjuvant, which not only relieves immunosuppression but also elicits robust antitumor immunity, is reported. Peritumorally injected Zn‐LDH sustainably neutralizes acidic TME and releases abundant Zn2+, promoting a pro‐inflammatory network composed of M1‐tumor‐associated macrophages, cytotoxic T cells, and natural‐killer cells. Moreover, the Zn‐LDH internalized by tumor cells effectively disrupts endo‐/lysosomes to block autophagy and induces mitochondrial damage, and the released Zn2+ activates the cGas‐STING signaling pathway to induce immunogenic cell death, which further promotes the release of tumor‐associated antigens to induce antigen‐specific cytotoxic T lymphocytes. Unprecedentedly, merely injection of Zn‐LDH adjuvant, without using any cytotoxic inflammatory cytokines or immune agonists, significantly inhibits the growth, recurrence, and metastasis of solid tumors in mice. This study provides a rational bottom‐up design of potent adjuvant for cancer metalloimmunotherapy against solid tumors.

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Section: Resultsmentioning

confidence: 99%

A Peritumorally Injected Immunomodulating Adjuvant Elicits Robust and Safe Metalloimmunotherapy against Solid Tumors

Zhang

Zhao

et al. 2022

Advanced Materials

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“…LITT’s primary mechanism of action is the induction of ablative hyperthermia and subsequent coagulative necrosis 1 . This report is the first demonstration of how LITT fundamentally changes the immune landscape of GBM during treatment.…”

Section: Discussionmentioning

confidence: 80%

“…9 In vitro and mouse studies on hyperthermia and its effects on the antitumor immune response point to a need for a better understanding of how LITT may mechanistically impact immune responses in patients. 1 Prospective clinical studies using LITT and immunotherapy will allow us to correlate these mechanisms to patient survival and optimize immunotherapy for GBM. Our case is the first human clinical presentation of increased CD8 T-cell infiltration and PD-L1 expression in post-LITT tissue (Fig.…”

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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“…It appears that LITT causes a disruption of tight junctions in the BBB, allowing increased access to large molecules such as doxorubicin, and a phase II study showed increased overall survival in patients treated with LITT + chemotherapy for HGG compared to the control group, with even better results in the group that started therapy later ( 23 , 24 ). Hyperthermia changes cytokine and chemokine production, enhancing antigen presentation as well as cytotoxic activity of T-cells, natural killer cells, and phagocytosis ( 25 ), which constitute the immune response of the human body against the tumor. If chemotherapy is offered too early, it will probably reduce the immune response of the host against the tumor, which would explain why the results of the late-arm chemotherapy appear more relevant ( 24 ).…”

Section: Discussionmentioning

confidence: 99%

Laser interstitial thermal therapy (LITT) for pediatric patients affected by intracranial tumors

et al. 2023

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IntroductionThe surgical treatment of brain tumors has evolved over time, offering different strategies tailored to patients and their specific lesions. Among these strategies, Laser Interstitial Thermal Therapy (LITT) is one of the most recent advances in pediatric neurooncological surgery, and its results and evolution are still under assessment.MethodsWe retrospectively analyzed data from six pediatric patients with deep-seated brain tumors treated with LITT at a single center between November 2019 and June 2022. A total of four patients underwent a stereotaxic biopsy during the same operating session. The indications and preparation for LITT, technical issues, clinical and radiological follow-up, impact on quality of life, and oncological treatment are discussed.ResultsThe mean patient age eight years (ranging from 2 to 11 years). The lesion was thalamic in four patients, thalamo-peduncular in one, and occipital posterior periventricular in one. In total, two patients had been previously diagnosed with low-grade glioma (LGG). Biopsies revealed LGG in two patients, ganglioglioma grade I in one, and diffuse high-grade glioma (HGG) in one. Postoperatively, two patients presented with transient motor deficits. The mean follow-up period was 17 months (ranging from 5 to 32 months). Radiological follow-up showed a progressive reduction of the tumor in patients with LGG.ConclusionLaser interstitial thermal therapy is a promising, minimally invasive treatment for deep-seated tumors in children. The results of lesion reduction appear to be relevant in LGGs and continue over time. It can be used as an alternative treatment for tumors located at sites that are difficult to access surgically or where other standard treatment options have failed.

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

Cited by 29 publications

References 157 publications

A Peritumorally Injected Immunomodulating Adjuvant Elicits Robust and Safe Metalloimmunotherapy against Solid Tumors

A Peritumorally Injected Immunomodulating Adjuvant Elicits Robust and Safe Metalloimmunotherapy against Solid Tumors

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

Laser interstitial thermal therapy (LITT) for pediatric patients affected by intracranial tumors

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