ArticleCancer discovery2016
Immunogenomics of Hypermutated Glioblastoma: A Patient with Germline POLE Deficiency Treated with Checkpoint Blockade Immunotherapy.
Article in Cancer discovery, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04761744 (A Phase II Study of Nivolumab in Patients With Genetic Alterations in DNA Damage Repair and Response Who Progressed After Standard Treatment for Metastatic Solid Cancers), which is not on this map. Cited by 198 papers, 4 of them syntheses that pooled it.
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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.
A Phase II Study of Nivolumab in Patients With Genetic Alterations in DNA Damage Repair and Response Who Progressed After Standard Treatment for Metastatic Solid Cancers
Who cites it
198 citing papers in PubMed, 4 syntheses or guidelines pooled it, 291 citations in OpenAlex.
- ERK1/2 Phosphorylation Predicts Survival in Recurrent Glioblastoma Following Intracerebral and Adjuvant PD-1/CTLA-4 Immunotherapy: A REMARK-guided Analysis.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Pooled it
- Destabilizing the genome as a therapeutic strategy to enhance response to immune checkpoint blockade: a systematic review of clinical trials evidence from solid and hematological tumors.Frontiers in pharmacology · 2023Pooled it
- Impact of molecular and clinical variables on survival outcome with immunotherapy for glioblastoma patients: A systematic review and meta-analysis.CNS neuroscience & therapeutics · 2022Pooled it
- Integrated genomic analysis identifies a genetic mutation model predicting response to immune checkpoint inhibitors in melanoma.Cancer medicine · 2020Pooled it
- Neoadjuvant PD1 plus CTLA-4 immune checkpoint blockade in surgically resectable recurrent glioblastoma: a randomized surgical window-of-opportunity trial.Nature communications · 2026Trial
- Improved overall survival in an anti-PD-L1 treated cohort of newly diagnosed glioblastoma patients is associated with distinct immune, mutation, and gut microbiome features: a single arm prospective phase I/II trial.Nature communications · 2025Trial
- Randomized Phase II and Biomarker Study of Pembrolizumab plus Bevacizumab versus Pembrolizumab Alone for Patients with Recurrent Glioblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Trial
- Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma.Nature medicine · 2019Trial
- N2M2 (NOA-20) phase I/II trial of molecularly matched targeted therapies plus radiotherapy in patients with newly diagnosed non-MGMT hypermethylated glioblastoma.Neuro-oncology · 2019Trial
- Brain barriers at the crossroads of glioma immune surveillance and immunotherapy response.Nature reviews. Cancer · 2026Review
- Article
- Tumor infiltrating lymphocytes in glioblastoma: immunobiology and translational implications.NPJ precision oncology · 2026Review
- Tumor transcriptional state predicts survival in immune-checkpoint-blockade-treated glioblastoma.Nature cancer · 2026Article
- Review
- Heat up and Destroy: Immunotherapy of "Cold" Tumors Using the Example of Glioblastoma.International journal of molecular sciences · 2026Review
- From Classical to Emerging Biomarkers of Brain and Central Nervous System Tumors. An Evidence-Based Review with a Focus on Gliomas.Cellular and molecular neurobiology · 2026Review
- Germline variants in ATM, BRCA2, other cancer predisposition and novel candidate genes are implicated in glioma risk in adult glioma patients with a familial or personal history of tumors.Acta neuropathologica · 2026Article
- Biomarkers for predicting immunotherapy response and resistance in glioblastoma.Frontiers in immunology · 2026Review
- Genome instability and crosstalk with the immune response.Genome medicine · 2025Review
- Whole genome sequencing-based analysis of genetic predisposition to adult glioblastoma.NPJ genomic medicine · 2025Article
138 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
We present the case of a patient with a left frontal glioblastoma with primitive neuroectodermal tumor features and hypermutated genotype in the setting of a POLE germline alteration. During standard-of-care chemoradiation, the patient developed a cervical spine metastasis and was subsequently treated with pembrolizumab. Shortly thereafter, the patient developed an additional metastatic spinal lesion. Using whole-exome DNA sequencing and clonal analysis, we report changes in the subclonal architecture throughout treatment. Furthermore, a persistently high neoantigen load was observed within all tumors. Interestingly, following initiation of pembrolizumab, brisk lymphocyte infiltration was observed in the subsequently resected metastatic spinal lesion and an objective radiographic response was noted in a progressive intracranial lesion, suggestive of active central nervous system (CNS) immunosurveillance following checkpoint blockade therapy. SIGNIFICANCE: It is unclear whether hypermutated glioblastomas are susceptible to checkpoint blockade in adults. Herein, we provide proof of principle that glioblastomas with DNA-repair defects treated with checkpoint blockade may result in CNS immune activation, leading to clinically and immunologically significant responses. These patients may represent a genomically stratified group for whom immunotherapy could be considered. Cancer Discov; 6(11); 1230-6. ©2016 AACR.See related commentary by Snyder and Wolchok, p. 1210This article is highlighted in the In This Issue feature, p. 1197.
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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.