Tumor Treating Fields: killing two birds with one stone

Lee, Juyeun; Grabowski, Matthew M.; Lathia, Justin D.

doi:10.1172/jci159073

Cited by 9 publications

(12 citation statements)

References 18 publications

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“…The activity and status of immune cells are closely tied to the course of glioma [21]. In high-grade glioma species, the immune killing effects are often modulated by the tumor microenvironment (TME) and become debilitating [22]. As a result of tumor mutations, new antigens are produced, and the exposure of these antigens may provide new targeting opportunities for immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis Identified Glycosyltransferase Signature to Predict Glioma Prognosis and TAM Phenotype

Liu

et al. 2023

BioMed Research International

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Glycosylation is the most common posttranslational modification of proteins. Glycosyltransferase gene differential expression dictates the glycosylation model and is epigenetically regulating glioma progression and immunity. This study is aimed at identifying the glycosyltransferase gene signature to predict the prognosis and immune characteristics of glioma. The glycosyltransferase gene signature of glioma was identified in the TCGA database and validated in the CGGA database. Glioma patients were then divided into high- and low-risk groups based on risk scores to compare survival differences and predictive capacity. Subsequently, validation of glycosyltransferase gene signature merits by comparing with other signatures and utility in clinical judgment. The immune cell infiltration, immune pathways, and immune checkpoint expression level were also analyzed and compared in the high- and low-risk groups. Finally, the signature and its gene function were tested in our cohort and in vitro experiments. Eight glycosyltransferase genes were identified to establish the glycosyltransferase signature to predict the prognosis of glioma patients. The survival time was shorter in the high-risk group compared to the low-risk group based on glycosyltransferase signature and was confirmed in an independent external cohort. The glycosyltransferase signature displayed outstanding predictive capacity than other signatures in the TCGA and CGGA database cohorts. Furthermore, patients in the high-risk group were positively correlated with TAM infiltration, immune checkpoint expression level, and protumor immune pathways in TCGA cohorts. Validation of clinical tissue specimens revealed that the high-risk group was closely associated with infiltration of M2 TAMs. High-risk genes in the signature promote glioma proliferation, invasion, and macrophage recruitment in an in vitro validation of U87 and U251 cell lines. This carefully constructed that glycosyltransferase signature can predict the prognosis and immune profile of gliomas and help us evaluate subsequent macrophage-targeted therapies as well as other immune microenvironment modulation therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis Identified Glycosyltransferase Signature to Predict Glioma Prognosis and TAM Phenotype

Liu

et al. 2023

BioMed Research International

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“…TTF for GBM involves applying alternating electric fields at intermediate frequencies and requires that the therapy be performed for greater than 18 h per day in order to confer clinical benefit [ 11 , 24 ]. Multiple biomolecular mechanisms are involved in the antineoplastic effects of TTF [ 25 ]. The antimitotic effect is the most widely accepted mechanism, yet a myriad of other means have also been hypothesized and tested, including DNA-damage response, suppression of cancer cell migration, autophagy, innate immunity, and immunogenic cell death [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

“…In addition to the additive effects of TTF noted in combination with chemotherapy and radiation, TTF may also play an important role as an adjuvant treatment in immunotherapy trials by stabilizing tumor progression, thereby allowing patients to mount an immune response [ 6 , 14 ]. This is particularly relevant given the recent flurry of exciting results in the immunotherapy sphere for DIPG [ 6 , 7 , 8 , 25 ]. TTF are capable of stimulating antitumor immunity properties, which may further produce a synergistic effect in combination with immunotherapies [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

“…This is particularly relevant given the recent flurry of exciting results in the immunotherapy sphere for DIPG [ 6 , 7 , 8 , 25 ]. TTF are capable of stimulating antitumor immunity properties, which may further produce a synergistic effect in combination with immunotherapies [ 25 ]. As such, the combination of TTF with experimental treatment options may represent an exciting new avenue worthy of continued investigation.…”

Section: Discussionmentioning

confidence: 99%

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Positioning Transclival Tumor-Treating Fields for the Treatment of Diffuse Intrinsic Pontine Gliomas

Essayed

Jarvis

Bernstock

et al. 2023

Life

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Diffuse intrinsic pontine glioma (DIPG) carries an extremely poor prognosis, with 2-year survival rates of <10% despite the maximal radiation therapy. DIPG cells have previously been shown to be sensitive to low-intensity electric fields in vitro. Accordingly, we sought to determine if the endoscopic endonasal (EE) implantation of an electrode array in the clivus would be feasible for the application of tumor-treating fields (TTF) in DIPG. Anatomic constraints are the main limitation in pediatric EE approaches. In our Boston Children’s Hospital’s DIPG cohort, we measured the average intercarotid distance (1.68 ± 0.36 cm), clival width (1.62 ± 0.19 cm), and clival length from the base of the sella (1.43 ± 0.69 cm). Using a linear regression model, we found that only clival length and sphenoid pneumatization were significantly associated with age (R2 = 0.568, p = 0.005 *; R2 = 0.605, p = 0.0002 *). Critically, neither of these parameters represent limitations to the implantation of a device within the dimensions of those currently available. Our findings confirm that the anatomy present within this age group is amenable to the placement of a 2 × 1 cm electrode array in 94% of patients examined. Our work serves to demonstrate the feasibility of implantable transclival devices for the provision of TTFs as a novel adjunctive therapy for DIPG.

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“…Given the special immune environment of intracranial tumors, brain malignancies suppress immune cells activity and anti-cancer function, and revitalizing central immune system has become the emerging for malignant brain tumors and experienced tremendous growth [2]. Considering the transformation of tumors under TTFields exposure to a state more favorable for anti-tumor immune response [47], and its role of switching on the BBB, TTFields may potentially enhance the central anti-tumor immune response [54,82]. At present, immunotherapeutic approaches for GBM contain: vaccines, checkpoint inhibitors, CAR-T cells, and oncolytic viruses [2].…”

Section: Preclinical Studies Of Ttfields In Malignant Brain Tumorsmentioning

confidence: 99%

Therapeutic Potential of Tumor Treating Fields for Malignant Brain Tumors

Zhou

Xing

Zhou

et al. 2023

Preprint

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Background Malignant brain tumors are among the most threatening diseases of the central nervous system, and despite increasingly updated treatments, the prognosis has not been improved. Tumor treating fields (TTFields) are an emerging approach in cancer treatment using intermediate-frequency and low-intensity electric field, and can lead to development of novel therapeutic options. Recent findings A series of biological processes induced by TTFields to exert anti-cancer effects have been identified, and applications of TTFields in oncology have been increasingly reported. This review addresses the mechanisms of TTFields and recent advances in the application of TTFields therapy in malignant brain tumors, especially in glioblastoma (GBM). Conclusions As a novel therapeutic strategies, TTFields have shown promising results in many clinical trials, especially in GBM, and continue to evolve. A growing number of patients with malignant brain tumors are being enrolled in ongoing clinical studies demonstrating that TTFields-based combination therapies can improve treatment outcomes.

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Tumor Treating Fields: killing two birds with one stone

Cited by 9 publications

References 18 publications

Comprehensive Analysis Identified Glycosyltransferase Signature to Predict Glioma Prognosis and TAM Phenotype

Comprehensive Analysis Identified Glycosyltransferase Signature to Predict Glioma Prognosis and TAM Phenotype

Positioning Transclival Tumor-Treating Fields for the Treatment of Diffuse Intrinsic Pontine Gliomas

Therapeutic Potential of Tumor Treating Fields for Malignant Brain Tumors

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