ArticleCancer immunology, immunotherapy : CII2021
High tumor mutational burden and T-cell activation are associated with long-term response to anti-PD1 therapy in Lynch syndrome recurrent glioblastoma patient.
Article in Cancer immunology, immunotherapy : CII, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 2 of them syntheses that pooled it.
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Who cites it
25 citing papers in PubMed, 2 syntheses or guidelines pooled it, 45 citations in OpenAlex.
- A systematic review of immunotherapy in high-grade glioma: learning from the past to shape future perspectives.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Pooled it
- Systematic Review of Molecular Targeted Therapies for Adult-Type Diffuse Glioma: An Analysis of Clinical and Laboratory Studies.International journal of molecular sciences · 2023Pooled it
- Case Report: Concordance of cerebrospinal fluid-derived circulating tumor DNA with tumor tissue in spinal glioblastoma associated with Lynch syndrome.Frontiers in oncology · 2026Article
- The anti-aging Klotho protects glioblastoma macrophages from radiotherapy-induced inflammation and predicts immunotherapy response.International journal of cancer · 2025Article
- Unique Genetic and Epigenetic Alterations in Glioblastoma Long-Term Survivors: Insights From Two Clinical Cases.Journal of cellular and molecular medicine · 2025Article
- Polyclonal expansion of functional tumor-reactive lymphocytes infiltrating glioblastoma for personalized cell therapy.Nature communications · 2025Article
- A long-term glioblastoma survivor with Lynch syndrome: a case report of tumor molecular and microenvironment characterization.Discover oncology · 2025Article
- Single-cell and spatial atlas of glioblastoma heterogeneity: characterizing theFrontiers in immunology · 2025Article
- Towards Effective Treatment of Glioblastoma: The Role of Combination Therapies and the Potential of Phytotherapy and Micotherapy.Current issues in molecular biology · 2024Review
- Case report: Temozolomide induced hypermutation indicates an unfavorable response to immunotherapy in patient with gliomas.Frontiers in immunology · 2024Article
- Lynch Syndrome-Associated Glioblastoma Treated With Concomitant Chemoradiotherapy and Immune Checkpoint Inhibitors: Case Report and Review of Literature.Brain tumor research and treatment · 2024Article
- Molecular Targeted Therapies in Glioblastoma Multiforme: A Systematic Overview of Global Trends and Findings.Brain sciences · 2023Review
- Cellular and molecular features related to exceptional therapy response and extreme long-term survival in glioblastoma.Cancer medicine · 2023Review
- A novel prognostic related lncRNA signature associated with amino acid metabolism in glioma.Frontiers in immunology · 2023Article
- Characteristics of glioblastomas and immune microenvironment in a Chinese family with Lynch syndrome and concurrent porokeratosis.Frontiers in oncology · 2023Article
- Article
- Durable benefit and change in TCR clonality with nivolumab in a Lynch syndrome-associated glioma.Therapeutic advances in medical oncology · 2022Article
- Integrated machine learning methods identify FNDC3B as a potential prognostic biomarker and correlated with immune infiltrates in glioma.Frontiers in immunology · 2022Article
- Review
- Brain Cancers in Genetic Syndromes.Current neurology and neuroscience reports · 2021Review
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGlioblastomas (GBMs) in patients harboring somatic or germinal mutations of mismatch-repair (MMR) genes exhibit a hypermutable phenotype. Here, we describe a GBM patient with increased tumor mutational burden and germline MMR mutations, treated using anti-PD1 therapy.
methodsA woman with newly diagnosed GBM (nGBM) was treated by surgery, radiotherapy, and temozolomide. The tumor recurred after 13 months leading to a second surgery and treatment with nivolumab. Whole-exome sequencing was performed on the nGBM, recurrent GBM (rGBM), and blood. Immune infiltration was investigated by immunohistochemistry and the immune response in the blood during treatment was analyzed by flow cytometry.
resultsHigh density of infiltrating CD163 + cells was found in both GBM specimens. Large numbers of CD3 + and CD8 + T cells were homogeneously distributed in the nGBM. The infiltration of CD4 + T cells and a different CD8 + T cell density were observed in the rGBM. Both GBM shared 12,431 somatic mutations, with 113 substitutions specific to the nGBM and 1,683 specific to the rGBM. Germline variants included pathogenic mutation in the MSH2 (R359S) gene, suggesting the diagnosis of Lynch syndrome. Systemic immunophenotyping revealed the generation of CD8 + T memory cells and persistent activation of CD4 + T cells. The patient is still receiving nivolumab 68 months after the second surgery.
conclusionsOur observations indicate that the hypermutator phenotype associated with germinal mutations of MMR genes and abundant T-cell infiltration contributes to a durable clinical benefit sustained by a persistent and robust immune response during anti-PD1 therapy.
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