Journal articleJ Immunother Cancer · March 24, 2026
BACKGROUND: Glioblastoma (GBM) remains uniformly lethal due to pronounced intratumoral heterogeneity and a highly immunosuppressive microenvironment that limits the efficacy of targeted therapies. METHODS: We engineered chimeric antigen receptor (CAR) T ce ...
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Journal articleClin Cancer Res · February 17, 2026
PURPOSE: Exhaustion represents a collection of programmed T-cell differentiation states and an important mode of T-cell dysfunction. T-cell progression from progenitor to terminal exhaustion is associated with upregulation of the transcription factor thymo ...
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Journal articleVaccines (Basel) · November 30, 2025
High-grade gliomas (HGGs) and diffuse midline gliomas (DMGs) in pediatric patients carry a poor prognosis, necessitating the rapid development of novel therapies. Peptide vaccines represent a safe, repeatable, and rational immunotherapeutic modality aimed ...
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Journal articleNeuro Oncol · October 1, 2025
This review explores the pivotal role of preanalytical variables in bringing liquid biopsy approaches into the clinic for brain tumors. Preanalytical variables encompass a range of critical issues, from blood sample collection and handling to the impact of ...
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Journal articleNat Cancer · September 2025
The human cytomegalovirus (CMV) antigen pp65 is expressed in high-grade glioma (HGG) and medulloblastoma but not in the adjacent brain. This single-arm phase 1 trial ( NCT03299309 ) assessed the safety and immunogenicity of a peptide vaccine (PEP-CMV) targ ...
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Journal articleNeurooncol Adv · September 2025
Immunotherapies have thus far proved of limited efficacy against glioblastoma. Failures can be attributed to a host of immunosuppressive mechanisms that are either directly employed by the tumor or are instead a convenient feature of the intracranial envir ...
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Journal articleFASEB J · June 30, 2025
Brain atrophy is a common feature of neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and more recently SARS-CoV-2 infection for which the neuroinflammatory mechanism is not fully understood. Nevertheless ...
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Journal articleJ Clin Invest · June 16, 2025
The efficacy of T cell-activating therapies against glioma is limited by an immunosuppressive tumor microenvironment and tumor-induced T cell sequestration. We investigated whether peripherally infused nonantigen specific autologous lymphocytes could accum ...
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Journal articlebioRxiv · April 12, 2025
Tumor-infiltrating lymphocyte (TIL) therapy, recently approved by the FDA for melanoma, is an emerging modality for cell-based immunotherapy. However, its application in immunologically 'cold' tumors such as glioblastoma remains limited due to sparse T cel ...
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Journal articleImmunity · January 14, 2025
Whereas terminally exhausted T (Tex_term) cells retain anti-tumor cytotoxic functions, the frequencies of stem-like progenitor-exhausted T (Tex_prog) cells better reflect immunotherapeutic responsivity. Here, we examined the intratumoral cellular interacti ...
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Journal articleNeuron · June 19, 2024
Microglial calcium signaling is rare in a baseline state but strongly engaged during early epilepsy development. The mechanism(s) governing microglial calcium signaling are not known. By developing an in vivo uridine diphosphate (UDP) fluorescent sensor, G ...
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Journal articleNeuro Oncol · May 3, 2024
BACKGROUND: Myeloid cells comprise up to 50% of the total tumor mass in glioblastoma (GBM) and have been implicated in promoting tumor progression and immunosuppression. Modulating the response of myeloid cells to the tumor has emerged as a promising new a ...
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Journal articleBrain · February 1, 2024
Cerebral malaria is the deadliest complication that can arise from Plasmodium infection. CD8 T-cell engagement of brain vasculature is a putative mechanism of neuropathology in cerebral malaria. To define contributions of brain endothelial cell major histo ...
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Journal articleBrain Behav Immun · August 2023
The contribution of circulating verses tissue resident memory T cells (TRMs) to clinical neuropathology is an enduring question due to a lack of mechanistic insights. The prevailing view is TRMs are protective against pathogens in the brain. However, the e ...
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Journal articleMol Psychiatry · July 2023
Chemogenetic approaches using Designer Receptors Exclusively Activated by Designer Drugs (DREADD, a family of engineered GPCRs) were recently employed in microglia. Here, we used Cx3cr1CreER/+:R26hM4Di/+ mice to express Gi-DREADD (hM4Di) on CX3CR1+ cells, ...
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Journal articleCancer Immunol Res · June 2, 2023
Glioblastoma (GBM) is the most common malignant brain tumor in adults, responsible for approximately 225,000 deaths per year. Despite preclinical successes, most interventions have failed to extend patient survival by more than a few months. Treatment with ...
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Journal articleNeurooncol Adv · 2023
BACKGROUND: The nervous and immune systems interact in a reciprocal manner, both under physiologic and pathologic conditions. Literature spanning various CNS pathologies including brain tumors, stroke, traumatic brain injury and de-myelinating diseases des ...
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Journal articleInnovation in Aging · December 20, 2022
AbstractSurgical parabiosis is widely used to study the mechanistic influence of the circulating milieu on aging and regeneration. This powerful model presents diverse complications based on age, strain, sex ...
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Journal articleNat Commun · September 27, 2022
Cellular senescence is a plausible mediator of inflammation-related tissue dysfunction. In the aged brain, senescent cell identities and the mechanisms by which they exert adverse influence are unclear. Here we used high-dimensional molecular profiling, co ...
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Journal articleFrontiers in Aging · January 1, 2022
Surgical parabiosis enables sharing of the circulating milieu between two organisms. This powerful model presents diverse complications based on age, strain, sex, and other experimental parameters. Here, we provide an optimized parabiosis protocol for the ...
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Journal articleSci Immunol · November 12, 2021
Severe coronavirus disease 2019 (COVID-19) pneumonia survivors often exhibit long-term pulmonary sequelae, but the underlying mechanisms or associated local and systemic immune correlates are not known. Here, we have performed high-dimensional characteriza ...
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Journal articleFrontiers in Oncology · October 28, 2021
Glioblastoma (GBM) is the most common primary brain tumor in adults an carries and carries a terrible prognosis. The current regiment of surgical resection, radiation, and chemotherapy has remained largely unchanged in recent years as new therapeutic appro ...
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Journal articleJ Clin Invest · July 1, 2021
Clinical immunotherapy approaches are lacking efficacy in the treatment of glioblastoma (GBM). In this study, we sought to reverse local and systemic GBM-induced immunosuppression using the Helicobacter pylori neutrophil-activating protein (NAP), a potent ...
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Journal articleFront Immunol · 2021
CD8 T cell infiltration of the central nervous system (CNS) is necessary for host protection but contributes to neuropathology. Antigen presenting cells (APCs) situated at CNS borders are thought to mediate T cell entry into the parenchyma during neuroinfl ...
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Journal articleNeuro Oncology Advances · January 1, 2021
The GL261 cell line, syngeneic on the C57BL/6 background, has, since its establishment half a century ago in 1970, become the most commonly used immunocompetent murine model of glioblastoma. As immunotherapy has entered the mainstream of clinical discourse ...
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Journal articleBrain · December 1, 2020
Immunosuppression of unknown aetiology is a hallmark feature of glioblastoma and is characterized by decreased CD4 T-cell counts and downregulation of major histocompatibility complex class II expression on peripheral blood monocytes in patients. This immu ...
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Journal articleSci Immunol · November 6, 2020
Lower respiratory viral infections, such as influenza virus and severe acute respiratory syndrome coronavirus 2 infections, often cause severe viral pneumonia in aged individuals. Here, we report that influenza viral pneumonia leads to chronic nonresolving ...
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Journal articleJ Immunol · September 1, 2020
Theiler's murine encephalomyelitis virus (TMEV) infection of the CNS is cleared in C57BL/6 mice by a CD8 T cell response restricted by the MHC class I molecule H-2Db The identity and function of the APC(s) involved in the priming of this T cell response is ...
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Journal articleNat Commun · June 24, 2020
The application of adoptive T cell therapies, including those using chimeric antigen receptor (CAR)-modified T cells, to solid tumors requires combinatorial strategies to overcome immune suppression associated with the tumor microenvironment. Here we test ...
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Journal articleCurr Opin Virol · April 2020
The innate immune system is the first line of defense against infections with pathogens. It provides direct antiviral mechanisms to suppress the viral life cycle at multiple steps. Innate immune cells are specialized to recognize pathogen infections and ac ...
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Journal articleHum Gene Ther · December 2019
There are many kidney diseases that might be addressed by gene therapy. However, gene delivery to kidney cells is inefficient. This is due, in part, to the fact that the kidney excludes molecules above 50 kDa and that most gene delivery vectors are megaDal ...
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Journal articleNeuro-Oncology · November 11, 2019
AbstractSystemic immunosuppression following neurological insults including stroke, traumatic brain injury, and glioblastoma (GBM) causes mortality and leads to failure of immune-modulating therapies. Exact ...
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Journal articleJCI Insight · April 4, 2019
Antibody-mediated lymphoablation is used in solid organ and stem cell transplantation and autoimmunity. Using murine anti-thymocyte globulin (mATG) in a mouse model of heart transplantation, we previously reported that the homeostatic recovery of CD8+ T ce ...
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Journal articleBlood · February 14, 2019
Chimeric antigen receptor T (CAR-T) cell therapy is a new pillar in cancer therapeutics; however, its application is limited by the associated toxicities. These include cytokine release syndrome (CRS) and neurotoxicity. Although the IL-6R antagonist tocili ...
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Journal articleAm J Transplant · May 2018
Prolonged cold ischemia storage (CIS) is a leading risk factor for poor transplant outcome. Existing strategies strive to minimize ischemia-reperfusion injury in transplanted organs, yet there is a need for novel approaches to improve outcomes of marginal ...
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Journal articleJCI Insight · February 22, 2018
Recipient endogenous memory T cells with donor reactivity pose an important barrier to successful transplantation and costimulatory blockade-induced graft tolerance. Longer ischemic storage times prior to organ transplantation increase early posttransplant ...
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Journal articleFront Oncol · 2018
Glioblastoma (GBM) is a lethal cancer of the central nervous system with a median survival rate of 15 months with treatment. Thus, there is a critical need to develop novel therapies for GBM. Immunotherapy is emerging as a promising therapeutic strategy. H ...
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Journal articleSci Rep · December 18, 2017
We previously showed increased growth associated protein 43 (GAP-43) expression in brain samples resected from patients with cortical dysplasia (CD), which was correlated with duration of epilepsy. Here, we used a rat model of CD to examine the regulation ...
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Journal articleAm J Transplant · August 2017
Lymphoablation is routinely used in transplantation, and its success is defined by the balance of pathogenic versus protective T cells within reconstituted repertoire. While homeostatic proliferation and thymopoiesis may both cause T cell recovery during l ...
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Journal articleFront Immunol · 2017
Memory T cells are characterized by their low activation threshold, robust effector functions, and resistance to conventional immunosuppression and costimulation blockade. Unlike their naïve counterparts, memory T cells reside in and recirculate through pe ...
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Journal articleJ Immunol · April 1, 2016
Ab-mediated lymphoablation is commonly used in solid organ and hematopoietic cell transplantation. However, these strategies fail to control pathogenic memory T cells efficiently and to improve long-term transplant outcomes significantly. Understanding the ...
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Journal articleBlood · February 26, 2015
Following injury, platelets rapidly interact with the exposed extracellular matrix (ECM) of the vessel wall and the surrounding tissues. Hyaluronan (HA) is a major glycosaminoglycan component of the ECM and plays a significant role in regulating inflammati ...
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Journal articleAm J Transplant · February 2015
Donor-reactive memory T cells undermine organ transplant survival and are poorly controlled by immunosuppression or costimulatory blockade. Memory CD4 T cells provide CD40-independent help for the generation of donor-reactive effector CD8 T cells and alloa ...
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Journal articleAm J Transplant · March 2013
Antibody-mediated lymphocyte depletion is frequently used as induction therapy in sensitized transplant patients. Although T cells with an effector/memory phenotype remain detectable after lymphoablative therapies in human transplant recipients, the role o ...
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Journal articleThe Journal of Immunology · May 1, 2012
AbstractAntithymocyte globulin (ATG) is a lymphoablative agent used in transplant patients. In this study, we tested how murine analog of ATG (mATG)affects pre-existent donor-reactive memory T cells. mATG ...
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Journal articleJ Vis Exp · September 13, 2010
Several well-known morphogenetic gradients and cellular movements occur along the dorsal/ventral axis of the Drosophila embryo. However, the current techniques used to view such processes are somewhat limited. The following protocol describes a new techniq ...
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