A5085331050- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Glioma Diagnosis and Treatment
- Immune cells in cancer
- Cancer Research and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Chemokine receptors and signaling
- Immunotherapy and Immune Responses
- Inflammatory mediators and NSAID effects
- Cancer Cells and Metastasis
- Cerebral Venous Sinus Thrombosis
- Cancer, Stress, Anesthesia, and Immune Response
- Trigeminal Neuralgia and Treatments
- Cancer, Hypoxia, and Metabolism
- Intracranial Aneurysms: Treatment and Complications
- Ocular Surface and Contact Lens
- Intensive Care Unit Cognitive Disorders
- Intraocular Surgery and Lenses
- RNA Interference and Gene Delivery
- Intracerebral and Subarachnoid Hemorrhage Research
- Pharmacological Effects and Toxicity Studies
- Nanoplatforms for cancer theranostics
- Epilepsy research and treatment
- Venous Thromboembolism Diagnosis and Management
- Ocular Infections and Treatments
Duke Medical Center
2021-2025
Johns Hopkins Medicine
2018-2024
Johns Hopkins University
2018-2024
Duke University
2021
Duke University Hospital
2021
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...
Significance There is an urgent need for improved cancer immunotherapies. The nanoparticles described here deliver genes to stimulate the immune system specifically kill tumor cells. This synthetic, biodegradable avoids use of common gene delivery materials like viruses that can have safety concerns and manufacturing limitations. Local nanoparticle evades adverse side effects stemming from systemic administration immune-activating therapeutics. Importantly, this technology causes a...
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 an aggressive and heterogeneous brain tumor characterized by extensive plasticity, which contributes to resistance against conventional therapies. To address this challenge, we generated a unique single nuclei RNA sequencing atlas, integrating GBM, normal tissue, developmental datasets. Utilizing single-cell (scRNA-seq) analysis methods, comprehensively GBM heterogeneity focusing on identifying homogeneous cell surface antigens suitable for chimeric antigen...
Nanomedicine can improve traditional therapies by enhancing the controlled release of drugs at targeted tissues in body. However, there still exists disease- and therapy-specific barriers that limit efficacy such treatments. A major challenge developing effective for one most aggressive brain tumors, glioblastoma (GBM), is affecting cancer cells while avoiding damage to surrounding healthy parenchyma. Here, we developed poly(ethylene glycol) (PEG)-poly(beta-amino ester) (PBAE)...
Abstract BACKGROUND Sacrificing the superior petrosal vein (SPV) is controversial during a microvascular decompression (MVD). There have been multiple reports of complications including life-threatening brainstem infarction and cerebellar edema. OBJECTIVE To analyze potential for vascular when SPV sacrificed an MVD. METHODS Retrospective chart review was performed to identify all MVDs trigeminal neuralgia hemifacial spasm from 2007 2018 at 1 institution. Cases with ≥1 mo follow-up were...
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...
Trigeminal neuralgia (TN) is a neuropathic pain disorder characterized by severe, lancinating facial that commonly treated with medication, percutaneous rhizotomy, and/or microvascular decompression (MVD). Patients who are not found to have distinct arterial compression during MVD present management challenge. In 2013, the authors reported on small case series of such patients in whom glycerin was injected intraoperatively into cisternal segment trigeminal nerve. The objective authors' study...
INTRODUCTION: Stroke is a leading cause of death and long-term disability worldwide. Acute ischemia results in profound inflammatory response that counterproductive to short- recovery. Programmed Death Protein 1 (PD-1) an immune checkpoint has been shown be upregulated after acute cerebral injury, and—upon binding its ligand PD-L1—negatively regulates cells limit the response. METHODS: C57BL/6J mice underwent middle artery occlusion (MCAO) were randomized into three arms: (1)sham surgery,...
<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>
<p>Figure S6: Ccr6 ablation delays tumor growth across multiple models and CCR6CCL20 expression correlates with overall survival in cancer patients.</p>
<p>Figure S3: Ccr6-/- Tregs are transcriptionally and metabolically distinct from WT Tregs.</p>
INTRODUCTION: Glioblastoma is an extremely aggressive form of brain cancer and despite the many advances made in therapeutic options, outcome quality life remains poor. Fibroblasts have been demonstrated to play a role various systemic cancers by remodeling reprogramming tumor microenvironment immunologically metabolically. Recently, cancer-associated fibroblasts (CAFs) identified glioblastoma (GBM) patients there reason believe that CAFs may protumoral effect GBM progression. METHODS: Nine...
Abstract Glioblastoma (GBM) is an aggressive primary tumor of the brain with a dismal prognosis for patients. Despite standard care treatment, median survival 12–15 months. The blockade inhibitory checkpoints such as PD-1 and CTLA-4 has become mainstay immunotherapy to treat solid tumors but it lacks efficacy in treating GBM Emergence alternative on T cells mechanism acquired resistance considered one major hurdles success anti-PD-1 therapy GBM. Using orthotopic mouse model GBM, we have seen...
Xia, Yuanxuan BA; Kim, Timothy Y BS; Mashouf, Leila A Patel, Kisha K; Xu, Risheng AB, AM, MD, PhD; Casaos, Joshua Eileen; Hung, Alice L Sc.B., Adela Wu A.B.; Garzon-Muvdi, Tomas MS; Bender, Matthew T MD; Jackson, Christopher M Bettegowda, Chetan Lim, Michael MD Author Information