Very low mutation burden is a feature of inflamed recurrent glioblastomas responsive to cancer immunotherapy.
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Several immunotherapy clinical trials in recurrent glioblastoma have reported long-term survival benefits in 10-20% of patients. Here we perform genomic analysis of tumor tissue from recurrent WHO grade IV glioblastoma patients acquired prior to immunotherapy intervention. We report that very low tumor mutation burden is associated with longer survival after recombinant polio virotherapy or after immune checkpoint blockade in recurrent glioblastoma patients. A relationship between tumor mutation burden and survival is not observed in cohorts of immunotherapy naïve newly diagnosed or recurrent glioblastoma patients. Transcriptomic analyses reveal an inverse relationship between tumor mutation burden and enrichment of inflammatory gene signatures in cohorts of recurrent, but not newly diagnosed glioblastoma tumors, implying that a relationship between tumor mutation burden and tumor-intrinsic inflammation evolves upon recurrence.
Neoplasm Recurrence, Local
Proportional Hazards Models
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Outcome Assessment, Health Care
Published Version (Please cite this version)10.1038/s41467-020-20469-6
Publication InfoGromeier, Matthias; Brown, Michael C; Zhang, Gao; Lin, Xiang; Chen, Yeqing; Wei, Zhi; ... Ashley, David M (2021). Very low mutation burden is a feature of inflamed recurrent glioblastomas responsive to cancer immunotherapy. Nature communications, 12(1). pp. 352. 10.1038/s41467-020-20469-6. Retrieved from https://hdl.handle.net/10161/22380.
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Rory David Deutsch Distinguished Professor of Neuro-Oncology
Dr. Ashley's primary research focus is laboratory based, investigating the role of immunotherapy as a novel approach to the treatment of tumors of the central nervous system (CNS). Since beginning his appointment at the faculty level at Duke in August of 1995 his activities have centered on two main areas of investigation. The first involves both in vivo and in vitro studies of the use of molecular therapeutics to target a CNS tumor associated antigen. The second area of interest comprises a det
James B. Powell, Jr. Distinguished Professor of Pediatric Oncology, in the School of Medicine
Overview: Our laboratory is pursuing a comprehensive analysis of the biology and therapy of adult and childhood central nervous system malignancies, particularly high-grade medulloblastoma, glioma, and ependymoma. Laboratory Studies: Active programs, using human adult and pediatric CNS tumor continuous cell lines, transplantable xenografts growing subcutaneously and intracranially in athymic nude mice and rats, and as well as in the subarachnoid space of the ath
Professor of Neurosurgery
I am a classically trained virologist with a focus on molecular mechanisms of RNA virus pathogenesis. My career is dedicated to unraveling RNA virus:host relations and devising methods of exploiting them for cancer immunotherapy and vaccine design. My background is in translation regulation and mRNA metabolism, viral RNA sensing and innate immunity, and cancer immunology and immunotherapy. Basic mechanistic research in my laboratory is supporting an ambitious clinical translational research prog
Associate Professor in Pathology
Professor of Neurosurgery
I am a professor of medicine, a medical oncologist at Duke's Preston Robert Tisch Brain Tumor Center as well as the Deputy Director of the Center for Cancer Immunotherapy, Duke Cancer Institute, where are tasked to speed up clinical research and translation for scientists across all departments and across all tumor types at Duke, who have made discoveries that show promise for developing new immunotherapies. Prior to joining Duke in September, 2019, I worked as a medical oncologi
Professor of Pathology
Brain tumors are diagnosed in more than 20,000 Americans annually. The most malignant neoplasm, glioblastoma, is also the most common. Similarly, brain tumors constitute the most common solid neoplasm in children and include astrocytomas of the cerebellum, brain stem and cerebrum as well as medulloblastomas of the cerebellum. My colleagues and I have endeavored to translate the bench discoveries of genetic mutations and aberrant protein expressions found in brain tumors to better understan
Professor in Surgery
I have 22 years of experience in the field of cancer vaccines and immunotherapy and I am an accomplished T cell immunologist. Laboratory website:https://surgery.duke.edu/immunology-inflammation-immunotherapy-laboratory Current projects in the Nair Laboratory:1] Dendritic cell vaccines using tumor-antigen encoding RNA (mRNA, total tumor RNA, amplified tumor mRNA)<br
Associate Professor of Neurosurgery
Dr. Katy Peters, MD PhD FAAN is an associate professor of neurology at the Preston Robert Tisch Brain Tumor Center (PRTBTC) at Duke. Her academic medical career started at Stanford University School of Medicine where received a MD and PhD in Cancer Biology. After completing a neurology residency at Johns Hopkins University along with a fellowship in cognitive neurosciences, Katy joined the PRTBTC as a neuro-oncology fellow. In 2009, she became a faculty member at PRTBTC.
Robert H., M.D. and Gloria Wilkins Professor of Neurosurgery, in the School of Medicine
Current research activities involve the immunotherapeutic targeting of a tumor-specific mutation in the epidermal growth factor receptor. Approaches used to target this tumor-specific epitope include unarmed and radiolabeled antibody therapy and cell mediated approaches using peptide vaccines and dendritic cells. Another area of interest involves drug delivery to brain tumors. Translational and clinical work is carried out in this area to formulate the relationship between various direct intratu
Henry S. Friedman Distinguished Professor of Neuro-Oncology in the School of Medicine
Our research activities center on the molecular genetics and biology of cancer with a focus on the identification, characterization, and therapeutic targeting of driver mutations involved in the genesis and progression of brain cancers. Gliomas are the most common type of primary brain tumor. Through genomic studies, we have identified mutations in IDH1 and IDH2 in 70% of progressive malignant gliomas. These are somatic missense mutations that alter a conserved arginine residue and gain a
Assistant Professor of Neurosurgery
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