A5013524951- Immune cells in cancer
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- RNA Interference and Gene Delivery
- Virus-based gene therapy research
- Cancer, Hypoxia, and Metabolism
- Nanoplatforms for cancer theranostics
- Glioma Diagnosis and Treatment
- Brain Metastases and Treatment
- Cancer Research and Treatments
- Immune Cell Function and Interaction
- Neuroinflammation and Neurodegeneration Mechanisms
- Metabolomics and Mass Spectrometry Studies
- Adenosine and Purinergic Signaling
- Lung Cancer Treatments and Mutations
- Lung Cancer Research Studies
- Tryptophan and brain disorders
- T-cell and B-cell Immunology
- Adipose Tissue and Metabolism
- Phagocytosis and Immune Regulation
- Nanoparticle-Based Drug Delivery
- Epigenetics and DNA Methylation
- HER2/EGFR in Cancer Research
- Monoclonal and Polyclonal Antibodies Research
Northwestern University
2016-2024
Neurological Surgery
2016-2024
Northwestern Medicine
2021-2022
Midwestern University
2022
University of Chicago
2015
Data Harbor (United States)
2015
University of Illinois Chicago
2015
The mechanisms by which regulatory T cells (Tregs) migrate to and function within the hypoxic tumor microenvironment are unclear. Our studies indicate that specific ablation of hypoxia-inducible factor 1α (HIF-1α) in Tregs results enhanced CD8+ cell suppression versus wild-type under hypoxia, due increased pyruvate import into mitochondria. Importantly, HIF-1α-deficient minimally affected inhibition lipid oxidation, a fuel is critical for Treg metabolism tumors. Under HIF-1α directs glucose...
Abstract The NLRP3 inflammasome is linked to sterile and pathogen-dependent inflammation, its dysregulation underlies many chronic diseases. Mitochondria have been implicated as regulators of the through several mechanisms including generation mitochondrial reactive oxygen species (ROS). Here, we report that electron transport chain (ETC) complex I, II, III V inhibitors all prevent activation. Ectopic expression Saccharomyces cerevisiae NADH dehydrogenase (NDI1) or Ciona intestinalis...
Abstract As a key component of the standard care for glioblastoma, radiotherapy induces several immune resistance mechanisms, such as upregulation CD47 and PD-L1. Here, leveraging these radiotherapy-elicited processes, we generate bridging-lipid nanoparticle (B-LNP) that engages tumor-associated myeloid cells (TAMCs) to glioblastoma via anti-CD47/PD-L1 dual ligation. We show engager B-LNPs block PD-L1 promote TAMC phagocytic activity. To enhance subsequent T cell recruitment antitumor...
Abstract The potent immunosuppression induced by glioblastoma (GBM) is one of the primary obstacles to finding effective immunotherapies. One hallmark GBM-associated immunosuppressive landscape massive infiltration myeloid-derived suppressor cells (MDSC) and, a lesser extent, regulatory T (Treg) within tumor microenvironment. Here, we showed that B (Breg) are prominent feature GBM microenvironment in both preclinical models and clinical samples. Forty percent patients (n = 60) scored...
Tumor-associated myeloid cells (TAMCs) are key drivers of immunosuppression in the tumor microenvironment, which profoundly impedes clinical response to immune-dependent and conventional therapeutic modalities. As a hallmark glioblastoma (GBM), TAMCs massively recruited reach up 50% brain mass. Therefore, they have recently been recognized as an appealing target blunt GBM with hope maximizing outcome antitumor therapies. Here we report nano-immunotherapy approach capable actively targeting...
Glioma-associated myeloid cells generate polyamines to survive and function within the acidic tumor microenvironment.
Immunotherapy has revolutionized the treatment of many tumors. However, most glioblastoma (GBM) patients have not, so far, benefited from such successes. With goal exploring ways to boost anti-GBM immunity, we developed a B cell–based vaccine (BVax) that consists 4-1BBL+ cells activated with CD40 agonism and IFNγ stimulation. BVax migrates key secondary lymphoid organs is proficient at antigen cross-presentation, which promotes both survival functionality CD8+ T cells. A combination...
Combination therapy has become a cornerstone in cancer treatment to potentiate therapeutic effectiveness and overcome drug resistance metastasis. In this work, we explore combination trials breast brain metastasis (BCBM), highlighting deficiencies trial design underlining promising strategies. On October 31, 2019, examined ClinicalTrials.gov for interventional clinical involving BCBM, without limiting date or location. Information on characteristics was collected. therapies used were...
Understanding the spatial relationship and functional interaction of immune cells in glioblastoma (GBM) is critical for developing new therapeutics that overcome highly immunosuppressive tumor microenvironment. Our study showed B T form clusters within GBM microenvironment a 15-μm radius, suggesting could synapses GBM. However, GBM-infiltrating suppress activation CD8 + cells. To this immunosuppression, we leveraged B-cell functions by activating them with CD40 agonism, IFNγ, BAFF to...
Glioblastoma (GBM) is a highly aggressive and malignant brain tumor with limited therapeutic options poor prognosis. Despite current treatments, the invasive nature of GBM often leads to recurrence. A promising alternative strategy harness potential immune system against cells. Our previous data showed that Bvax (B-cell-based vaccine) can induce responses in preclinical models GBM. In this study, we aim characterize antigenic reactivity BVax-derived antibodies evaluate their potential. We...
Fatty acid (FA) metabolism directly influences the functional capabilities of T cells in tumor microenvironments. Thus, developing tools to interrogate FA-uptake by cell subsets is important for understanding immunosuppression. Herein, we have generated a novel FA-Qdot 605 dye conjugate with superior sensitivity and flexibility any previously commercially available alternatives. For first time, demonstrate that this nanoparticle can be used as specific measure fatty uptake both in-vitro...
A paucity of chemotherapeutic options for metastatic brain cancer limits patient survival and portends poor clinical outcomes. Using a CNS small-molecule inhibitor library 320 agents known to be blood-brain barrier permeable approved by the FDA, we interrogated breast metastasis vulnerabilities identify an effective agent. Metixene, antiparkinsonian drug, was identified as top therapeutic agent that capable decreasing cellular viability inducing cell death across different subtypes. This...
Abstract Background Breast cancer brain metastases (BCBM) are the final frontier in neuro-oncology for which more efficacious therapies required. In this work, we explore clinical trials BCBM, and determine shortcomings development of new BCBM to shed light on potential areas enhancement. Methods On July 9, 2018, searched ClinicalTrials.gov all interventional therapeutic involving without limiting date or location. Information trial characteristics, including phase, status, start end dates,...
Oncolytic virotherapy is a treatment approach with increasing clinical relevance, as indicated by the marked survival benefit seen in animal models and its current exploration human patients cancer. The use of an adenovirus vector for this therapeutic modality common, has significant animals, efficacy recently been linked to anti-tumor immune response that occurs following tumor antigen presentation. Here, we analyzed adaptive system's viral infection comparing replication-incompetent...