A5088152612- Cancer Immunotherapy and Biomarkers
- Glioma Diagnosis and Treatment
- CAR-T cell therapy research
- Immune cells in cancer
- Immunotherapy and Immune Responses
- Adenosine and Purinergic Signaling
- Nanoplatforms for cancer theranostics
- Cancer Research and Treatments
- Cancer Cells and Metastasis
- MicroRNA in disease regulation
- Cancer, Stress, Anesthesia, and Immune Response
- Chemokine receptors and signaling
- Neuroinflammation and Neurodegeneration Mechanisms
- Cancer, Hypoxia, and Metabolism
- Nanowire Synthesis and Applications
- Brain Metastases and Treatment
- Immune Cell Function and Interaction
- interferon and immune responses
- Meningioma and schwannoma management
- COVID-19 diagnosis using AI
- Machine Learning in Materials Science
- 3D Printing in Biomedical Research
- Neurofibromatosis and Schwannoma Cases
- Anesthesia and Neurotoxicity Research
- Advanced Electron Microscopy Techniques and Applications
Johns Hopkins Medicine
2019-2024
Johns Hopkins University
2019-2024
Sidney Kimmel Comprehensive Cancer Center
2020-2024
Bloomberg (United States)
2020-2024
Stanford University
2023
University of Baltimore
2020
Oxford University Press (United Kingdom)
2020
Whitehead Institute for Biomedical Research
2016-2018
Immunotherapy has revolutionized the treatment of cancers. Reinvigorating lymphocytes with checkpoint blockade become a cornerstone immunotherapy for multiple tumor types, but glioblastoma not yet shown clinical efficacy. A major hurdle to treat GBM is high degree myeloid-mediated immunosuppression in brain tumors that limits CD8 T-cell activity. potential strategy improve anti-tumor efficacy against glioma use myeloid-modulating agents target immunosuppressive cells, such as myeloid-derived...
Clinical trials involving anti-programmed cell death protein-1 (anti-PD-1) failed to demonstrate improved overall survival in glioblastoma (GBM) patients. This may be due the expression of alternative checkpoints such as B- and T- lymphocyte attenuator (BTLA) on several immune types including regulatory T cells. Murine GBM models indicate that there is significant upregulation BTLA tumor microenvironment (TME) with associated exhaustion. We investigate use antibodies against PD-1 reversing...
Acute cerebral ischemia triggers a profound inflammatory response. While macrophages polarized to an M2-like phenotype clear debris and facilitate tissue repair, aberrant or prolonged macrophage activation is counterproductive recovery. The inhibitory immune checkpoint Programmed Cell Death Protein 1 (PD-1) upregulated on precursors (monocytes) in the blood after acute cerebrovascular injury. To investigate therapeutic potential of PD-1 activation, we immunophenotyped circulating monocytes...
Abstract Glioblastoma (GBM) is a highly aggressive brain tumor with poor prognosis and high recurrence rates. The complex immune microenvironment of GBM infiltrated by tumor-associated microglia macrophages (TAM). TAMs are known to be heterogeneous in their functional metabolic states can transmit either protumoral or antitumoral signals glioma cells. Here, we performed bulk RNA sequencing single-cell on samples from patients GBM, which revealed increased ATP synthase expression oxidative...
INTRODUCTION: Cancer cells preferentially utilize aerobic glycolysis (Warburg effect). Recent studies show similar metabolic reprogramming in immune of the tumor microenvironment (TME). Heme oxygenase-1 (HMOX-1), a regulatory gene, is known to be upregulated glioblastoma (GBM) myeloid cells, but how HMOX-1 specifically modulates immunosuppression and energy utilization remains poorly understood. METHODS: Syngeneic glioma models with C57BL/6J mice implanted CT-2A were treated intracranial...
Pneumonia is one of the largest infectious diseases that cause death in children and elderly people across globe. impacts all young people's families everywhere but most prevalent Sub-Saharan Africa South Asia. In December 2019 Wuhan, a city China was affected by deadly, gruesome which declared pandemic World Health Organisation. But reason for outbreak not clear to everyone. Later, doctors identified disease as new species coronavirus, also currently known COVID-19. The main motivation...
Abstract BACKGROUND Cerebral vasospasm is a major source of morbidity and mortality following aneurysm rupture has limited treatment options. OBJECTIVE To evaluate the role programmed death-1 (PD-1) in cerebral vasospasm. METHODS Endovascular internal carotid artery perforation (ICAp) was used to induce mice. therapeutic potential targeting PD-1, death ligand-1 (PD-L1) administered 1 h after ICAp measured histologically at level ICA bifurcation bilaterally. PD-1 expressing immune cell...
Immune checkpoint inhibitors such as anti-programmed cell death protein 1 (anti-PD-1) have shown promise for the treatment of cancers melanoma, but results glioblastoma (GBM) been disappointing thus far. It has suggested that GBM multiple mechanisms immunosuppression, indicating a need combinatorial strategies. is well understood increases glutamate in tumor microenvironment (TME); however, significance this not understood. The authors posit upregulation TME immunosuppressive. utilized novel...
OBJECTIVE In this single-institution retrospective cohort study, the authors evaluated effect of dexamethasone on postoperative complications and overall survival in patients with glioma undergoing resection. METHODS A total 435 who underwent resection a primary were included study. The inclusion criterion was all at tertiary medical center between 2014 2019. RESULTS use both pre- demonstrated trend toward development wound infections (3% vs 0% single or no use, p = 0.082). No association...
Abstract Regulatory T cells (Treg) are important players in the tumor microenvironment. However, mechanisms behind their immunosuppressive effects poorly understood. We found that CCR6–CCL20 activity tumor-infiltrating Tregs is associated with greater glycolytic and ablation of Ccr6 reduced glycolysis lactic acid production while increasing compensatory glutamine metabolism. Immunosuppressive toward CD8+ was abrogated Ccr6−/− due to reduction activation-induced glycolysis. Furthermore, mice...
Introduction Despite the advent of immunotherapy as a promising therapeutic, glioblastoma (GBM) remains resistant to using checkpoint blockade due its highly immunosuppressive tumor milieu. Moreover, current anti-PD-1 treatment requires multiple infusions with adverse systemic effects. Therefore, we used PCL:PEG:PCL polymer gel loaded and implanted at site lymph nodes in an attempt maximize targeting inactivated T cells well mitigate unnecessary exposure.Methods Mice orthotopically GL261...
Atypical teratoid rhabdoid tumors (ATRTs) are aggressive pediatric brain with no current standard of care and an estimated median patient survival 12 to 18 months. Previous genetic analyses have implicated cyclin D1 enhancer zeste homolog 2 (EZH2), a histone methyltransferase that is in many cancers, as key drivers tumorigenicity ATRTs. Since the effects EZH2 facilitated by host cyclin-dependent kinases (CDKs), authors sought investigate potential therapeutic targeting CDKs ATRTs multi-CDK...
<p>Figure S2: CCR6 expression is enhanced in tumor-infiltrating Tregs co-expressing checkpoints and Ccr6 ablation reduces immunosuppressive phenotype.</p>
<p>Figure S5: Ccr6 ablation reduces Treg immunosuppression of CD8 T cells in the context tumor growth.</p>
<p>Figure S4: Ccr6-/- Tregs have reduced glycolysis compared to WT Tregs.</p>
<div>Abstract<p>Regulatory T cells (Treg) are important players in the tumor microenvironment. However, mechanisms behind their immunosuppressive effects poorly understood. We found that CCR6–CCL20 activity tumor-infiltrating Tregs is associated with greater glycolytic and ablation of <i>Ccr6</i> reduced glycolysis lactic acid production while increasing compensatory glutamine metabolism. Immunosuppressive toward CD8<sup>+</sup> was abrogated...
<p>Figure S1: CCR6 and CCL20 expression is increased in multiple tumors.</p>