ArticleThe Journal of clinical investigation2022
Tumor Treating Fields dually activate STING and AIM2 inflammasomes to induce adjuvant immunity in glioblastoma.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07383649 (Initial Safety Lead-in Followed by a Phase II Trial to Study Anti- HCMV Therapy in Breast Cancer Patients With Progressive Intracranial Metastases and CMV Infection), which is not on this map. Cited by 108 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Initial Safety Lead-in Followed by a Phase II Trial to Study Anti- HCMV Therapy in Breast Cancer Patients With Progressive Intracranial Metastases and CMV Infection (The Breast CMV Study)
Who cites it
108 citing papers in PubMed, 1 synthesis or guideline pooled it, 121 citations in OpenAlex.
- Association of Tumor Treating Fields (TTFields) therapy with survival in newly diagnosed glioblastoma: a systematic review and meta-analysis.Journal of neuro-oncology · 2023Pooled it
- Tumor-targeted interferon-α gene therapy for glioblastoma: a phase 1 trial.Nature medicine · 2026Trial
- Laser interstitial thermal therapy and adjuvant pembrolizumab in recurrent high-grade astrocytoma: a Phase 1/randomized Phase 2b trial.Nature communications · 2026Trial
- Tumor Treating Fields With Gemcitabine and Nab-Paclitaxel for Locally Advanced Pancreatic Adenocarcinoma: Randomized, Open-Label, Pivotal Phase III PANOVA-3 Study.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Trial
- Tumor Treating Fields (TTFields) sensitize anti-PD1-resistant lung tumors to PD1 blockade and remodel myeloid and lymphoid states.Research square · 2026Article
- cGAS-STING axis: A central regulator of neural homeostasis and neuroinflammatory pathogenesis.Neural regeneration research · 2026Article
- Tumor Treating Fields and the Glioblastoma Microenvironment: Mechanistic Convergences with Radiotherapy.Cancers · 2026Review
- Efficacy and immunogenic effects of Tumor Treating Fields (TTFields) in preclinical models of pancreatic ductal adenocarcinoma, with and without gemcitabine/nab-paclitaxel.International journal of cancer · 2026Article
- Microstructural MRI combined with metabolic MRI to evaluate the progression-free survival of patients with glioblastoma at the early follow-up after tumor treating fields: a pilot study.BMC medical imaging · 2026Article
- Post-recurrence management of malignant glial brain tumors: therapeutic strategies, evidence and limitations, palliative care, terminal sedation, and end-of-life considerations.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Review
- Inflammasomes in glioblastoma.Journal of neuroinflammation · 2026Review
- Micronuclei: origins, assays, mechanisms, diseases and treatments.Signal transduction and targeted therapy · 2026Review
- DNA delivered by lipid nanoparticles induces CD8+ T cell-dependent antitumor responses and enhances anti-PD-L1 therapy.JCI insight · 2026Article
- Opportunities and challenges of targeting cGAS-STING in cancer.Nature reviews. Cancer · 2026Review
- Tumor treating fields for newly diagnosed glioblastoma: a retrospective analysis.Journal of neuro-oncology · 2026Article
- Electricity-Based Locoregional Cancer Therapies and Their Associated Drug Delivery Technologies: From Principles of Action to Clinical Implications.Biomaterials research · 2026Review
- Translating physical stress into biological signals: precision electro-oncology based on conformational changes of electro-sensitive receptors and parameterized immune remodeling.Frontiers in oncology · 2026Review
- Tumor Treating Fields (TTFields), and their concomitant application with FOLFOX, are effective for the treatment of gastric cancer cells.Frontiers in oncology · 2026Article
- Development and Preliminary Validation of a Wearable Tumor Treating Fields Device for Breast Cancer Therapy.Breast cancer (Dove Medical Press) · 2026Article
48 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Tumor Treating Fields (TTFields), an approved therapy for glioblastoma (GBM) and malignant mesothelioma, employ noninvasive application of low-intensity, intermediate-frequency, alternating electric fields to disrupt the mitotic spindle, leading to chromosome missegregation and apoptosis. Emerging evidence suggests that TTFields may also induce inflammation. However, the mechanism underlying this property and whether it can be harnessed therapeutically are unclear. Here, we report that TTFields induced focal disruption of the nuclear envelope, leading to cytosolic release of large micronuclei clusters that intensely recruited and activated 2 major DNA sensors - cyclic GMP-AMP synthase (cGAS) and absent in melanoma 2 (AIM2) - and their cognate cGAS/stimulator of interferon genes (STING) and AIM2/caspase 1 inflammasomes to produce proinflammatory cytokines, type 1 interferons (T1IFNs), and T1IFN-responsive genes. In syngeneic murine GBM models, TTFields-treated GBM cells induced antitumor memory immunity and a cure rate of 42% to 66% in a STING- and AIM2-dependent manner. Using single-cell and bulk RNA sequencing of peripheral blood mononuclear cells, we detected robust post-TTFields activation of adaptive immunity in patients with GBM via a T1IFN-based trajectory and identified a gene panel signature of TTFields effects on T cell activation and clonal expansion. Collectively, these studies defined a therapeutic strategy using TTFields as cancer immunotherapy in GBM and potentially other solid tumors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.