A5082027834- Glioma Diagnosis and Treatment
- Immune cells in cancer
- Tryptophan and brain disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Cancer, Stress, Anesthesia, and Immune Response
- CAR-T cell therapy research
- Cancer Cells and Metastasis
- Chemokine receptors and signaling
- Ferroptosis and cancer prognosis
- Virus-based gene therapy research
- Cancer Research and Treatments
- Stress Responses and Cortisol
- RNA Interference and Gene Delivery
- Single-cell and spatial transcriptomics
- Cancer, Hypoxia, and Metabolism
- Cancer-related cognitive impairment studies
- Brain Metastases and Treatment
- Epigenetics and DNA Methylation
- T-cell and B-cell Immunology
- Protein Degradation and Inhibitors
- interferon and immune responses
- Gut microbiota and health
Loyola University Medical Center
2007-2025
Neurological Surgery
2016-2025
Loyola University Chicago
2010-2025
Northwestern University
2015-2024
Boston Children's Museum
2023
Boston Children's Hospital
2023
The University of Texas MD Anderson Cancer Center
2021-2023
Indo-American Center
2022
Robert H. Lurie Comprehensive Cancer Center of Northwestern University
2016-2022
The University of Texas Health Science Center at Houston
2021
Abstract Purpose: Glioblastoma (GBM) is the most common form of malignant glioma in adults. Although protected by both blood–brain and blood–tumor barriers, GBMs are actively infiltrated T cells. Previous work has shown that IDO, CTLA-4, PD-L1 dominant molecular participants suppression GBM immunity. This includes IDO-mediated regulatory T-cell (Treg; CD4+CD25+FoxP3+) accumulation, interaction T-cell–expressed, with dendritic cell-expressed, CD80, as well tumor- and/or macrophage-expressed,...
In many aggressive cancers, such as glioblastoma multiforme, progression is enabled by local immunosuppression driven the accumulation of regulatory T cells (Treg) and myeloid-derived suppressor (MDSC). However, mechanistic details how Tregs MDSCs are recruited in various tumors not yet well understood. Here we report that macrophages microglia within glioma microenvironment produce CCL2, a chemokine critical for recruiting both CCR4+ Treg CCR2+Ly-6C+ monocytic this disease setting. murine...
Abstract Purpose: Glioblastoma multiforme (GBM) is an aggressive adult brain tumor with a poor prognosis. One hallmark of GBM the accumulation immunosuppressive and tumor-promoting CD4+FoxP3+GITR+ regulatory T cells (Tregs). Here, we investigated role indoleamine 2,3 dioxygenase (IDO) in tumors impact on Treg recruitment. Experimental Design: To determine clinical relevance IDO expression tumors, first correlated patient survival to level from resected glioma specimens. We also used novel...
The blood-brain barrier (BBB) remains a formidable obstacle in medicine, preventing efficient penetration of chemotherapeutic and diagnostic agents to malignant gliomas. Here, transactivator transcription (TAT) peptide-modified gold nanoparticle platform (TAT-Au NP) with 5 nm core size is demonstrated be capable crossing the BBB efficiently delivering cargoes such as anticancer drug doxorubicin (Dox) Gd(3+) contrast brain tumor tissues. Treatment mice bearing intracranial glioma xenografts...
Abstract Purpose: Glioblastoma is the most aggressive primary brain tumor in adults with a median survival of 15–20 months. Numerous approaches and novel therapeutics for treating glioblastoma have been investigated setting phase III clinical trials, including recent analysis immune checkpoint inhibitor, nivolumab (anti-PD-1), which failed to improve recurrent patient survival. However, rather than abandoning inhibitor treatment glioblastoma, has shown promise other types cancer, ongoing...
Abstract Abundant macrophage infiltration and altered tumor metabolism are two key hallmarks of glioblastoma. By screening a cluster metabolic small-molecule compounds, we show that inhibiting glioblastoma cell glycolysis impairs migration lactate dehydrogenase inhibitor stiripentol emerges as the top hit. Combined profiling functional studies demonstrate A (LDHA)-directed extracellular signal-regulated kinase (ERK) pathway activates yes-associated protein 1 (YAP1)/ signal transducer...
Glioblastoma-targeted drug delivery systems facilitate efficient of chemotherapeutic agents to malignant gliomas, while minimizing systemic toxicity and side effects. Taking advantage the fibrin deposition that is characteristic tumors, we constructed spherical, Cy7-labeled, targeting micelles glioblastoma through addition fibrin-binding pentapeptide, cysteine-arginine-glutamic acid-lysine-alanine, or CREKA. Conjugation CREKA peptide Cy7-micelles increased average particle size zeta...
Purpose: Indoleamine 2,3 dioxygenase 1 (IDO1) mediates potent immunosuppression in multiple preclinical models of cancer. However, the basis for elevated IDO1 expression human cancer, including most common primary malignant brain tumor adults, glioblastoma (GBM), is poorly understood. The major objective this study to address gap our understanding how contributes biology GBM, and whether its level a determinant GBM patient outcome.Experimental Design: Patient-resected Cancer Genome Atlas,...
In human vitiligo, cutaneous depigmentation involves cytotoxic activity of autoreactive T cells. It was hypothesized that can progress in the absence regulatory cells (Treg). The percentage Treg among skin infiltrating evaluated by immunoenzymatic double staining for CD3 and FoxP3, revealing drastically reduced numbers non-lesional, perilesional lesional vitiligo skin. Assessment circulating pool FACS analysis CD4, CD25, CD127 FoxP3 expression, mixed lymphocyte reactions presence sorted...
REVIEW article Front. Immunol., 15 May 2013Sec. Immunological Tolerance and Regulation Volume 4 - 2013 | https://doi.org/10.3389/fimmu.2013.00116
Background: Glioblastoma (GBM) is the most aggressive primary brain tumor in adults and associated with a median overall survival (mOS) of 16-21 months. Our previous work found negative association between advanced aging benefit after treatment immunotherapy an experimental model. Given recent phase III clinical success patients many types cancer, but not for GBM, we hypothesize that enhances immunosuppression contributes to lack efficacy improve mOS malignant glioma. Herein, compare...
CD73 is a novel immune checkpoint associated with adenosine metabolism that promotes tumor progression by suppressing antitumor response and promoting angiogenesis. The inhibition of CD73, in combination blockade, targeted therapy or conventional therapy, improves effects numerous preclinical mouse models cancer. Emerging evidence suggests the anti-CD73 blockade has promising clinical activity patients advanced solid tumors. In this review, we will discuss specific role on both cells...
Abstract Purpose: Wild-type isocitrate dehydrogenase–expressing glioblastoma (GBM) is the most common and aggressive primary brain tumor with a median age at diagnosis of ≥65 years. It accounts for approximately 90% all GBMs has overall survival (OS) <15 months. Although immune checkpoint blockade (ICB) therapy achieved remarkable benefits in variety malignancies, similar success yet to be GBM among phase III clinical trials date. Our study aimed understand relationship between...
The highly lethal brain cancer glioblastoma (GBM) poses a daunting challenge because the blood-brain barrier renders potentially druggable amplified or mutated oncoproteins relatively inaccessible. Here, we identify sphingomyelin phosphodiesterase 1 (SMPD1), an enzyme that regulates conversion of to ceramide, as actionable drug target in GBM. We show brain-penetrant antidepressant fluoxetine potently inhibits SMPD1 activity, killing GBMs, through inhibition epidermal growth factor receptor...
Abstract The symbiotic interactions between cancer stem cells and the tumor microenvironment (TME) are critical for progression. However, molecular mechanism underlying this symbiosis in glioblastoma (GBM) remains enigmatic. Here, we show that circadian locomotor output cycles kaput (CLOCK) its heterodimeric partner brain muscle ARNT-like 1 (BMAL1) glioma (GSC) drive immunosuppression GBM. Integrated analyses of data from transcriptome profiling, single-cell RNA sequencing, TCGA datasets,...
Larry Sherman, David Wainwright, Helmut Ponta, and Peter Herrlich Forschungszentrum Karlsruhe, Institut für Genetik, D-76021 Germany
Glioblastoma multiforme (GBM) is a highly malignant brain tumor with an average survival time of 15 months. Previously, we and others demonstrated that CD4+FoxP3+ regulatory T cells (Tregs) infiltrate human GBM as well mouse models recapitulate tumors. However, whether tumor-resident Tregs are thymus-derived natural (nTregs) or induced (iTregs), by the conversion conventional CD4+ cells, has not been established. To investigate this question, utilized i.c. implanted GL261 cell-based...