A5079081497- Glioma Diagnosis and Treatment
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Immune cells in cancer
- CAR-T cell therapy research
- MicroRNA in disease regulation
- Brain Metastases and Treatment
- Neuroinflammation and Neurodegeneration Mechanisms
- Immune Cell Function and Interaction
- Circular RNAs in diseases
- Cytokine Signaling Pathways and Interactions
- Cancer Mechanisms and Therapy
- Cancer Cells and Metastasis
- Meningioma and schwannoma management
- Cancer, Stress, Anesthesia, and Immune Response
- Cancer, Hypoxia, and Metabolism
- Cancer Research and Treatments
- interferon and immune responses
- Radiomics and Machine Learning in Medical Imaging
- Cytomegalovirus and herpesvirus research
- Nanoplatforms for cancer theranostics
- Ferroptosis and cancer prognosis
- Cancer Genomics and Diagnostics
- Adenosine and Purinergic Signaling
- RNA Interference and Gene Delivery
Northwestern University
2021-2025
Neurological Surgery
2014-2025
Midwestern University
2021-2025
The University of Texas MD Anderson Cancer Center
2015-2024
Northwestern Medicine
2021-2024
Northwestern University
2024
Robert H. Lurie Comprehensive Cancer Center of Northwestern University
2022-2024
Hudson Institute
2022
John Wiley & Sons (United States)
2022
The University of Texas Health Science Center at Houston
2018-2021
In order to examine the mechanisms by which clonal deletion of autoreactive T cells occurs, a peptide antigen was used induce antigen-reactive thymocytes in vivo. Mice transgenic for cell receptor (TCR) that reacts this contain progress from immature mature phenotype. Intraperitoneal administration mice results rapid CD4 + CD8 TCR lo thymocytes. Apoptosis cortical can be seen within 20 hours treatment. These provide direct evidence vivo role apoptosis development antigen-induced tolerance.
To address the mechanisms controlling T helper (Th) phenotype development, we used DO10, a transgenic mouse line that expresses alpha beta T-cell receptor from an ovalbumin-reactive hybridoma, as source of naive cells can be stimulated in vitro with ovalbumin peptide presented by defined antigen-presenting (APCs). We have examined role cytokines and APCs regulation Th development. Interleukin 4 (IL-4) directs development toward Th2 phenotype, stimulating IL-4 silencing IL-2 interferon gamma...
Immunologic targeting of tumor-specific gene mutations may allow precise eradication neoplastic cells without toxicity. Epidermal growth factor receptor variant III (EGFRvIII) is a constitutively activated and immunogenic mutation not expressed in normal tissues but widely glioblastoma multiforme (GBM) other neoplasms.A phase II, multicenter trial was undertaken to assess the immunogenicity an EGFRvIII-targeted peptide vaccine estimate progression-free survival (PFS) overall (OS) vaccinated...
Macrophages (MΦs)/microglia that constitute the dominant tumor-infiltrating immune cells in glioblastoma are recruited by tumor-secreted factors and induced to become immunosuppressive tumor supportive (M2). Glioma cancer stem (gCSCs) have been shown suppress adaptive immunity, but their role innate immunity with respect recruitment polarization of MΦs/microglia is unknown. The properties gCSCs were characterized based on elaborated MΦ inhibitory cytokine-1 (MIC-1), transforming growth...
Little is known about the immune performance and interactions of CNS microglia/macrophages in glioma patients. We found that were predominant cell infiltrating gliomas (∼1% total cells); others identified myeloid dendritic cells (DCs), plasmacytoid DCs, T cells. isolated analyzed functions CD11b/c+CD45+ glioma-infiltrating (GIMs) from postoperative tissue specimens Although GIMs expressed substantial levels Toll-like receptors (TLRs), they did not appear stimulated to produce...
Therapeutic targeting of the immune checkpoints cytotoxic T-lymphocyte-associated molecule-4 (CTLA-4) and PD-1/PD-L1 has demonstrated tumor regression in clinical trials, phase 2 trials are ongoing glioblastoma (GBM). Previous reports have suggested that responses more frequent patients with tumors express PD-L1; however, this been disputed. At issue is validation PD-L1 biomarker assays prognostic impact. Using immunohistochemical analysis, we measured incidence expression 94 GBM. We...
Abstract Purpose: The epidermal growth factor receptor (EGFR) is overexpressed in ∼50% to 60% of glioblastoma multiforme tumors, and the most common EGFR mutant, EGFRvIII, expressed 24% 67% cases. We sought determine whether expression either wild-type or mutant EGFRvIII an independent predictor overall patient survival. Experimental Design: Glioblastoma patients (n = 196) underwent a ≥95% volumetric tumor resection followed by conformal radiation. Their status was determined...
Glioblastomas are highly infiltrated by diverse immune cells, including microglia, macrophages, and myeloid-derived suppressor cells (MDSCs). Understanding the mechanisms which glioblastoma-associated myeloid (GAMs) undergo metamorphosis into tumor-supportive characterizing heterogeneity of cell phenotypes within glioblastoma subtypes, discovering new targets can help design efficient immunotherapies. In this study, we performed a comprehensive battery phenotyping, whole-genome microarray...
The epidermal growth factor receptor variant III deletion mutation, EGFRvIII, is expressed in ∼30% of primary glioblastoma and linked to poor long-term survival. Rindopepimut consists the unique EGFRvIII peptide sequence conjugated keyhole limpet hemocyanin. In previous phase II trials (ACTIVATE/ACT II), rindopepimut was well tolerated with robust EGFRvIII-specific immune responses promising progression-free overall This multicenter, single-arm clinical trial (ACT III) performed confirm...
Many tumors overexpress tumor-associated antigens relative to normal tissue, such as EGFR. This limits targeting by human T cells modified express chimeric antigen receptors (CAR) due potential for deleterious recognition of cells. We sought generate CAR(+) capable distinguishing malignant from based on the disparate density EGFR expression generating two CARs monoclonal antibodies that differ in affinity. with low-affinity nimotuzumab-CAR selectively targeted overexpressing EGFR, but...
Despite a multiplicity of clinical trials testing immune checkpoint inhibitors, the frequency expression potential predictive biomarkers is unknown in glioma.In this study, we profiled shared biomarker phenotypes. To clarify relationships among tumor mutational load (TML), mismatch repair (MMR), and expression, patients with glioma (n = 327), including glioblastoma (GBM) 198), whose samples had been submitted for analysis from 2009 to 2016. The calculation algorithm TML included...
Epidermal growth factor receptor variant III (EGFRvIII) is a tumor-specific mutation widely expressed in glioblastoma multiforme (GBM) and other neoplasms, but absent from normal tissues. Immunotherapeutic targeting of EGFRvIII could eliminate neoplastic cells more precisely may be inhibited by concurrent myelosuppressive chemotherapy like temozolomide (TMZ), which produces survival benefit GBM. A phase II, multicenter trial was undertaken to assess the immunogenicity an experimental...
Adenosine-to-inosine (A-to-I) RNA editing was recently shown to be abundant in the human transcriptome, affecting thousands of genes. Employing a bioinformatic approach, we identified significant global hypoediting Alu repetitive elements brain, prostate, lung, kidney, and testis tumors. Experimental validation confirmed this finding, showing significantly reduced sequences within MED13 transcripts brain tissues. Looking at specific recoding noncoding sites, including cancer-related genes,...
Abstract Purpose: The incidence of regulatory T cells (Treg) in intrinsic central nervous system malignancies is unknown. Immunotherapeutic approaches that inhibit the Treg population may be limited to a subset patients with gliomas. Our hypothesis only most malignant gliomas have prominent glioma-infiltrating contributes immunosuppressive biology and presence Tregs negative prognostic variable. Experimental Design: We measured 135 glial tumors (including all pathologic types) glioma...
The clinical significance of epidermal growth factor receptor variant III (EGFRvIII) expression in glioblastoma multiforme (GBM) and its relationship with other key molecular markers are not clear. We sought to evaluate the GBM subtypes as defined by EGFRvIII status.The was assessed immunohistochemistry 649 patients newly diagnosed GBM. These data were then examined conjunction phospho-intermediates (in a subset these patients) downstream AKT Ras pathways YKL-40 well known risk factors,...
Glioblastoma is highly enriched with macrophages, and osteopontin (OPN) expression levels correlate glioma grade the degree of macrophage infiltration; thus, we studied whether OPN plays a crucial role in immune modulation. Quantitative PCR, immunoblotting, ELISA were used to determine expression. Knockdown was achieved using complementary siRNA, shRNA, CRISPR/Cas9 techniques, followed by series vitro functional migration immunological assays. gene-deficient mice examine roles...
Overcoming the profound immunosuppression in patients with solid cancers has impeded efficacious immunotherapy. Signal transducers and activators of transcription 3 (STAT3) recently emerged as a potential target for effective immunotherapy, this study, we describe novel small molecule inhibitor STAT3 that can penetrate central nervous system (CNS) mice physiologically relevant doses vitro reverse tolerance immune cells isolated from glioblastoma multiforme (GBM) patients. Specifically, it...
The human cytomegalovirus (HCMV) and glioma symposium was convened on April 17, 2011 in Washington, DC, attended by oncologists virologists involved studying the relationship between HCMV gliomas. purpose of meeting to reach a consensus role pathology gliomas clarify directions for future research. First, group summarized data that describe how biology overlaps with key pathways cancer. Then, basis published ongoing research, reached there is sufficient evidence conclude sequences viral gene...
Exosomes can mediate a dynamic method of communication between malignancies, including those sequestered in the central nervous system and immune system. We sought to determine whether exosomes from glioblastoma (GBM)-derived stem cells (GSCs) induce immunosuppression. report that GSC-derived (GDEs) have predilection for monocytes, precursor macrophages. The GDEs traverse monocyte cytoplasm, cause reorganization actin cytoskeleton, skew monocytes toward suppresive M2 phenotype, programmed...
Abstract Conventional therapies for glioblastoma multiforme (GBM) fail to target tumor cells exclusively, such that their efficacy is ultimately limited by nonspecific toxicity. Immunologic targeting of tumor-specific gene mutations, however, may allow more precise eradication neoplastic cells. The epidermal growth factor receptor variant III (EGFRvIII) a consistent and mutation widely expressed in GBMs other neoplasms. safety immunogenicity dendritic cell (DC)–based vaccine the EGFRvIII...