A5102971730- Immunotherapy and Immune Responses
- Immune cells in cancer
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Cancer Immunotherapy and Biomarkers
- Polysaccharides and Plant Cell Walls
- Immune Response and Inflammation
- Monoclonal and Polyclonal Antibodies Research
- Fungal Biology and Applications
- Cell Adhesion Molecules Research
- Wound Healing and Treatments
- Psoriasis: Treatment and Pathogenesis
- Cytomegalovirus and herpesvirus research
- Immunodeficiency and Autoimmune Disorders
- Cancer Cells and Metastasis
- Dermatology and Skin Diseases
- Immune responses and vaccinations
- Systemic Lupus Erythematosus Research
- Inflammation biomarkers and pathways
- Hepatitis B Virus Studies
- Extracellular vesicles in disease
- Virus-based gene therapy research
- Cytokine Signaling Pathways and Interactions
- COVID-19 Impact on Reproduction
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
University of Louisville
2015-2024
James Graham Brown Foundation
2006-2021
University of Louisville Hospital
2007-2014
Zero to Three
2006
Nanjing Medical University
2003-2006
One of the defining characteristics a pre-metastatic niche, fundamental requirement for primary tumor metastasis, is infiltration immunosuppressive macrophages. How these macrophages acquire their phenotype remains largely unexplored. Here, we demonstrate that tumor-derived exosomes (TDEs) polarize toward an characterized by increased PD-L1 expression through NF-kB-dependent, glycolytic-dominant metabolic reprogramming. TDE signaling TLR2 and NF-κB leads to glucose uptake. TDEs also...
Macrophages have been linked to tumor initiation, progression, metastasis, and treatment resistance. However, the transcriptional regulation of macrophages driving protumor function remains elusive. Here, we demonstrate that transcription factor c-Maf is a critical controller for immunosuppressive macrophage polarization in cancer. controls many M2-related genes has direct binding sites within conserved noncoding sequence Csf-1r gene promotes M2-like macrophage–mediated T cell suppression...
Abstract Anti-tumor mAbs hold promise for cancer therapy, but are relatively inefficient. Therefore, there is a need agents that might amplify the effectiveness of these mAbs. One such agent β-glucan, polysaccharide produced by fungi, yeast, and grains, not mammalian cells. β-Glucans bound C receptor 3 (CR3) and, in concert with target-associated complement fragment iC3b, elicit phagocytosis killing yeast. may also promote iC3b-opsonized tumor cells engendered administration anti-tumor In...
Abstract Tumor-associated macrophages (TAM) with an alternatively activated phenotype have been linked to tumor-elicited inflammation, immunosuppression, and resistance chemotherapies in cancer, thus representing attractive target for effective cancer immunotherapy. In this study, we demonstrate that particulate yeast-derived β-glucan, a natural polysaccharide compound, converts polarized or immunosuppressive TAM into classically potent immunostimulating activity. This process is associated...
SARS coronavirus 2 (SARS-CoV-2) is a novel viral pathogen that causes clinical disease called 2019 (COVID-19). Although most COVID-19 cases are asymptomatic or involve mild upper respiratory tract symptoms, significant number of patients develop severe critical disease. Patients with commonly present pneumonia may progress to life-threatening acute distress syndrome (ARDS). also predisposed venous and arterial thromboses associated poorer prognosis. The study identified the emergence...
Abstract Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature myeloid that promote tumor progression. In this study, we demonstrated activation C-type lectin receptor, dectin-1, in MDSC differentially modulates the function different subsets. Yeast-derived whole β-glucan particles (WGP; ligand to engage and activate oral treatment vivo) significantly decreased weight splenomegaly tumor-bearing mice with reduced accumulation polymorphonuclear but not monocytic...
Despite the remarkable success of immunotherapy in many types cancer, pancreatic ductal adenocarcinoma has yet to benefit. Innate immune cells are critical anti-tumor immunosurveillance and recent studies have revealed that these populations possess a form memory, termed trained innate immunity, which occurs through transcriptomic, epigenetic, metabolic reprograming. Here we demonstrate yeast-derived particulate β-glucan, an inducer traffics pancreas, causes CCR2-dependent influx...
The beneficial properties of β-glucans have been recognized for centuries. Their proposed mechanisms action in cancer therapy occur via stimulation macrophages and priming innate neutrophil complement receptor 3 eliciting 3-dependent cellular cytotoxicity iC3b-opsonized tumor cells. current study is to investigate whether β-glucan has any effect on antitumor adaptive T-cell responses.We first examined the trafficking orally administered particulate yeast-derived its interaction with...
Promoting complement (C) activation may enhance immunological mechanisms of anti-tumor Abs for tumor destruction. However, C components, such as C5a, trigger inflammation, which can promote growth. We addressed the role C5a on growth by transfecting both human carcinoma and murine lymphoma with mouse C5a. In vitro kinetics control vector, or parental cells revealed no significant differences. Tumor-bearing mice C5a-transfected xenografted had significantly less burden compared vector tumors....
Polymorphonuclear neutrophils (PMNs), the main effectors of innate immune system, have rarely been considered as an anticancer therapeutic tool. However, recent investigations using animal models and preliminary clinical studies highlighted potential antitumor efficacy PMNs. In current study, we find that PMNs from some healthy donors naturally potent cancer-killing activity against 4 different human cancer cell lines. The killing appears to be cell-specific since did not kill primary normal...
Abstract Ab maturation as well memory B and plasma cell differentiation occur primarily in the germinal centers (GCs). Systemic lupus erythematosus (SLE) may develop a result of enhanced GC activity. Previous studies have shown that dysregulated STAT3 pathway is linked to pathogenesis. However, exact role regulating SLE disease progression has not been fully understood. In this study, we demonstrated signaling cells essential for formation maintenance response. Increased apoptosis...
Regulation of myeloid-derived suppressor cells (MDSC) by ongoing inflammation following repeated chemotherapy remain elusive. In this study, we show that a multidose clinical regimen gemcitabine (GEM) treatment enhances the immunosuppressive function monocytic MDSC (M-MDSC), although tumor development is delayed in E0771 tumor-bearing mice. Accordingly, effector IFN-γ-producing CD4 and CD8 T are significantly decreased microenvironment (TME) GEM-treated The conditioned medium differentiation...
Psoriasis recurrence is a clinically challenging issue. However, the underlying mechanisms haven't been fully understood.RNAseq analysis from affected skin of psoriatic patients treated with topical glucocorticoid (GC) different outcomes was performed. In addition, imiquimod (IMQ)-induced mouse psoriasis-like model used to mimic GC treatment in human psoriasis patients. Skin tissues and draining distant lymph nodes (LNs) were harvested for flow cytometry histology analyses.RNAseq revealed...
Combined β-glucan with anti-tumor mAb therapy has demonstrated therapeutic efficacy in murine tumor models. The current study was designed to compare the of various sources β-glucans. Our studies that yeast β-glucan, combination mAb, resulted significantly smaller burdens and achieved enhanced long-term survival compared alone or extracts from mushrooms. Further indicated particle superior mushroom inducing cytokine secretion, particularly IL-12 production dendritic cells (DCs). In addition,...
Plasmacytoid dendritic cells (pDCs) are specialized type I IFN producers, which play an important role in pathogenesis of autoimmune disorders. Dysregulated autoreactive B cell activation is a hallmark most diseases. This study was undertaken to investigate interactions between pDCs and cells. After coculture that recognize self-Ag small nuclear ribonucleoprotein particles with activated pDCs, we found significantly enhance proliferation, autoantibody production, survival response TLR BCR...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel viral pathogen that causes clinical disease called 2019 (COVID-19). Approximately 20% of infected patients experience severe manifestation the disease, causing bilateral pneumonia and distress syndrome. COVID-19 also have pronounced coagulopathy with approximately 30% experiencing thromboembolic complications. However, etiology driving remains unknown. Here, we explore whether prominent neutrophilia seen in contributes...