A5004594443- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Immune cells in cancer
- Phagocytosis and Immune Regulation
- Cancer Mechanisms and Therapy
- Cancer Research and Treatments
- CAR-T cell therapy research
- Wnt/β-catenin signaling in development and cancer
- Renal cell carcinoma treatment
- Dietary Effects on Health
- Adipokines, Inflammation, and Metabolic Diseases
- Ovarian cancer diagnosis and treatment
- Diet and metabolism studies
- Cancer-related gene regulation
- Glioma Diagnosis and Treatment
- Virus-based gene therapy research
- RNA Interference and Gene Delivery
- Inflammatory Biomarkers in Disease Prognosis
- Metabolism, Diabetes, and Cancer
- Cancer Cells and Metastasis
- Cancer Risks and Factors
- Adipose Tissue and Metabolism
- Cell death mechanisms and regulation
- Pancreatic and Hepatic Oncology Research
University of Alabama at Birmingham
2016-2024
O'Neal Comprehensive Cancer Center
2019-2024
Washington University in St. Louis
2004-2023
Sylvester Comprehensive Cancer Center
2018
University of Iowa
1997-2017
Iowa City Public Library
2013-2015
Fraternal Order of Eagles
2015
Iowa State University
1993
Dendritic cells (DC) have a critical effect on the outcome of adaptive immune responses against growing tumors. Whereas it is generally assumed that presence phenotypically mature DCs should promote protective antitumor immunity, evidence to contrary does exist. We describe here novel mechanism by which tumor-infiltrating dendritic (TIDC) actively contribute suppression CD8(+) T-cell-based immunity. Using BALB/NeuT model spontaneously arising mammary carcinoma, we found canonical MHC...
Antigen receptor engagement on T lymphocytes activates transcription factors important for stimulating cytokine gene expression. This is critical clonal expansion of antigen-specific cells and propagation immune responses. Additionally, under some conditions antigen stimulation initiates apoptosis through the induced expression CD95 ligand its receptor. Here we demonstrate that factor, NFAT, which inducible many genes, also plays a role in regulation cell receptor-mediated Two sites within...
Abstract Glioblastoma (GBM) is a lethal disease with no effective therapies available. We previously observed upregulation of the TAM (Tyro-3, Axl, and Mer) receptor tyrosine kinase family member AXL in mesenchymal GBM showed that knockdown induced apoptosis mesenchymal, but not proneural, glioma sphere cultures (GSC). In this study, we report BGB324, novel small molecule inhibitor AXL, prolongs survival immunocompromised mice bearing GSC-derived GBM-like tumors. show protein S (PROS1),...
Background Obesity is a major risk factor for renal cancer, yet our understanding of its effects on antitumor immunity and immunotherapy outcomes remains incomplete. Deciphering these associations critical, given the growing clinical use immune checkpoint inhibitors metastatic disease mounting evidence an obesity paradox in context cancer immunotherapies, wherein obese patients with have improved outcomes. Methods We investigated between host anti-programmed cell death (PD-1)-based both...
Stimulation of mature peripheral T cells by TCR engagement results in activation signals that drive induction cytokine gene expression and clonal expansion. However, under some conditions, the leads instead to apoptosis. Recent studies demonstrate TCR-stimulated apoptosis requires CD95 ligand on activated followed an interaction between receptor also expressed this population. The experiments reported study were designed address signaling events triggered are important for regulating...
Background The constellation of human inflammatory bowel disease (IBD) includes ulcerative colitis and Crohn's disease, which both display a wide spectrum in the severity pathology. One theory is that multiple genetic hits to host immune system may contribute susceptibility IBD. However, experimental proof this concept still lacking. Several mouse models each recapitulate some aspects IBD have utilized single gene defect induce colitis. none produced pathology clearly distinguishable as...
Abstract Obesity is a mounting health concern in the United States and associated with an increased risk for developing several cancers, including renal cell carcinoma (RCC). Despite this, little known regarding impact of obesity on antitumor immunity. Because dendritic cells (DC) are critical regulators immunity, we examined combined effects tumor outgrowth DC function. Using diet-induced (DIO) model, function was evaluated mice bearing orthotopic RCC tumor-free controls. Tumor-free DIO had...
Members of the NLR family can assemble inflammasome complexes with adaptor protein ASC and caspase-1 that result in activation release IL-1β IL-18. Although NLRC4 is known to have a protective role tumorigenesis, there an increased appreciation for inflammasome-independent actions NLRC4. Here, we utilized syngeneic subcutaneous murine model B16F10 melanoma explore tumor suppression. We found NLRC4-deficient mice exhibited enhanced growth was independent components caspase-1. Nlrc4 expression...
Obesity is one of the leading risk factors for developing renal cell carcinoma, an immunogenic tumor that treated clinically with immunostimulatory therapies. Currently, however, mechanisms linking obesity cancer incidence are unclear. Using a model diet-induced obesity, we found obese BALB/c mice orthotopic tumors had increased total frequencies myeloid-derived suppressor cells (MDSC) in and spleens by d14 post-tumor challenge, relative to lean counterparts. Renal from elevated...
Targeting immune checkpoint proteins has recently gained substantial attention due to the dramatic success of this strategy in clinical trials for some cancers. Inducible T-cell co-stimulator ligand (ICOSLG) is a member B7 family regulatory ligands, expression which cancer implicated disease progression regulation antitumor adaptive immunity. Although aberrant ICOSLG been reported glioma cells, underlying mechanisms that promote glioblastoma (GBM) remain elusive.Here, we investigated causal...
Nearly 70% of adults in the US are currently overweight or obese. Despite such high prevalence, impact obesity on anti-tumor immunity and immunotherapy outcomes remains incompletely understood, particularly patients with breast cancer. Here, we addressed these gaps knowledge using two murine models cancer combined diet-induced obesity. We report that increases CXCL1 concentrations mammary tumor microenvironment, driving CXCR2-mediated chemotaxis accumulation granulocytic myeloid-derived...
Objective Diet‐induced obesity has been shown to alter immune function in mice, but distinguishing the effects of from changes diet composition is complicated. It was hypothesized that immunological differences would exist between diet‐induced obese (DIO) and obese‐resistant (OB‐Res) mice fed same high‐fat (HFD). Methods BALB/c were either standard chow or HFD generate lean DIO OB‐Res respectively. Resulting analyzed for serum immunologic metabolic profiles cellular parameters. Results on...
Obesity is associated with aggressive prostate cancer. To explore whether weight loss favourably affects tumour biology and other outcomes, we undertook a presurgical trial among overweight obese men This single-blinded, two-arm randomised controlled explored outcomes of intervention (WLI) that promoted ∼1 kg per week via caloric restriction increased physical activity (PA). Forty overweight/obese clinically confirmed cancer were to the WLI presurgery or control arm; changes in weight, body...
Obesity adversely impacts overall and cancer‐specific survival among breast cancer patients. Preclinical studies demonstrate negative energy balance inhibits progression; however, feasibility effects in patients are unknown. A two‐arm, single‐blinded, randomized controlled weight‐loss trial was undertaken presurgery 32 overweight/obese, Stage 0–II The attention control arm (AC) received basic nutritional counseling upper‐body progressive resistance training whereas the weight loss...
Despite evidence that antitumor immunity can be protective against renal cell carcinoma (RCC), few patients respond objectively to immunotherapy and the disease is fatal once metastases develop. We asked what extent combinatorial with Adenovirus-encoded murine TNF-related apoptosis-inducing ligand (Ad5mTRAIL) plus CpG oligonucleotide, given at primary tumor site, would prove efficacious metastatic RCC. To quantitate growth in mice, we developed a luciferase-expressing Renca line, monitored...
Expression of MHC class II pathway proteins in ovarian cancer correlates with prolonged survival. Murine and human cells were treated epigenetic modulators - histone deacetylase inhibitors a DNA methyltransferase inhibitor. mRNA protein expression the evaluated by qPCR flow cytometry. Treatment entinostat azacytidine ID8 vitro increased levels Cd74, Ciita, H2-Aa, H2-Eb1. CD74 after treatment either agent. A dose dependent response was seen entinostat. Combination showed higher than single...
Background: The Wnt/β-catenin pathway is linked to tumorigenesis in a variety of tumors and promotes T cell exclusion resistance checkpoint inhibitors. We sought determine whether small molecule inhibitor this pathway, WNT974, would impair tumor growth, affect gene expression patterns, improve the immune response human murine ovarian cancer models. Methods: Human cells were treated with WNT974 vitro. RNAseq libraries constructed differences patterns between responders nonresponders compared...