A5042701229- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Cancer Immunotherapy and Biomarkers
- Immune cells in cancer
- CAR-T cell therapy research
- Immune Response and Inflammation
- Extracellular vesicles in disease
- Tryptophan and brain disorders
- Cancer-related molecular mechanisms research
- Monoclonal and Polyclonal Antibodies Research
- Dietary Effects on Health
- NF-κB Signaling Pathways
- Neuroinflammation and Neurodegeneration Mechanisms
- Ferroptosis and cancer prognosis
- Aquaculture disease management and microbiota
- PI3K/AKT/mTOR signaling in cancer
- Virus-based gene therapy research
- Cancer Research and Treatments
- Viral Infectious Diseases and Gene Expression in Insects
- Bacteriophages and microbial interactions
- MicroRNA in disease regulation
- Microbial infections and disease research
- Toxin Mechanisms and Immunotoxins
- Renal cell carcinoma treatment
Oregon State University
2002-2023
Providence Portland Medical Center
2005-2023
Rush University Medical Center
2011-2016
Sarepta Therapeutics (United States)
2015
Rush University
2012-2014
Bipar
2013
Cancer Research Center
2005-2010
Providence Regional Medical Center Everett
2006-2007
Oregon Health & Science University
2006
Abstract Acquisition of full T-cell effector function and memory differentiation requires appropriate costimulatory signals, including ligation the molecule OX40 (TNFRSF4, CD134). Tumors often grow despite presence tumor-specific T cells establish an environment with weak costimulation immune suppression. Administration agonists has been shown to significantly increase survival tumor-bearing mice was dependent on both CD4 CD8 during priming. To understand how work in established tumors, we...
We report that OX40 stimulation drives all lineages of CD4 T cell development, including regulatory cells (Tregs), and the plasticity response is dependant on local cytokines. In TGF-beta1-treated cultures, an agonist increased IFN-gamma IL-4 production diverted from Treg lineage. However, cytokine blockade in context promoted enhanced accumulation. This observation was evident naive mice, as engagement proliferation accumulation vivo. Lastly, administration influenced experimental...
Abstract There is growing evidence that engagement of OX40 (CD134), a member the TNF receptor superfamily, can directly stimulate antigen‐specific CD8 + T cells. It has been shown cells express following activation, but response to stimulation not fully characterized. We utilized an transgenic cell model (OT‐I) determine if boost generation memory. Our results demonstrate enhanced costimulation, via agonist anti‐OX40 antibody, increases CD25 and phospho‐Akt expression on significantly...
Abstract IL-18 induces inflammation resulting in either enhanced protection from pathogens or exacerbation of autoimmunity, and T cells are profoundly activated during these responses. How influences cell activation is unknown, but this study mice shows that boosted Ag-specific clonal expansion effector induced a subpopulation IFN-γ superproducing cells. Commitment to production through was independent NK IL-12 dependent on host-derived IFN-γ. To determine how effectors occurred, shown...
Melanoma is one of the few types cancer with an increasing annual incidence. While a number immunotherapies for melanoma have been associated significant clinical benefit, including high-dose IL-2 and cytotoxic T lymphocyte antigen 4 (CTLA-4) blockade, response to either these single agents has limited 11-20% treated patients. Therefore, in this study, we sought test hypothesis that combination CTLA-4 blockade could mediate more profound therapeutic response.Here, B6 mice were challenged...
Circulating cancer exosomes are microvesicles which originate from malignant cells and other organs influenced by the disease can be found in blood. The exosomal proteomic cargo often traced to they originated, reflecting physiological status of these cells. similarities between tumor exhibit potential vesicles as an invaluable target for liquid biopsies. Exosomes were isolated serum eight osteosarcoma-bearing dogs, five healthy dogs with traumatic fractures. We also characterized collected...
Engagement of OX40 greatly improves CD4 T cell function and survival. Previously, we showed that both engagement CTLA-4 blockade led to enhanced expansion, but only signaling increased To identify pathways associated with OX40-mediated survival, the gene expression Ag-activated cells isolated from mice treated anti-OX40 -CTLA-4 was compared. This comparison revealed a potential role for IL-12 through IL-12R-signaling subunit (IL-12Rbeta2) on activated 3 days previously Ag anti-OX40. The...
2,3,7,8-Tetrachlorodibenzo-<i>p</i>-dioxin (TCDD) suppresses many immune responses, both innate and adaptive. Suppression is mediated by the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor. The AhR mediates TCDD toxicity presumably through alteration of transcriptional events, either promoting gene expression or potentially physically interacting with other factors. Another factor, NF-κB/Rel, involved in several signaling pathways cells crucial for generating...
In patients with malignancy, the major barrier to achieving complete response is emergence of resistance current chemotherapeutic agents. One mechanisms by which tumour cells become resistant therapies altering cellular drug targets through mutations and/or deletions. Resistance this mechanism achieved more easily if has limited processes. We hypothesized that as Pseudomonas aeruginosa exotoxin T (ExoT) six proteins are required for cancer cell survival and proliferation, it highly unlikely...
Abstract OX40 agonists have potent immunotherapeutic effects against a variety of murine tumors, yet it is unclear the role that age-related immune senescence plays on their efficacy. We found middle-aged and elderly tumor-bearing mice (12 20 mo old, respectively) treated with anti-OX40 were less responsive compared young 6 or age. Decreased tumor-free survival was observed in both male female mice, not due to changes surface expression T cells older animals. Enumeration cytokine-producing...
Immune responses wane during aging, posing challenges to the potential effectiveness of cancer immunotherapies. We previously demonstrated that in context a promising immunotherapeutic, OX40 agonist (αOX40), older animals exhibited impaired anti-tumor immune and diminished CD4 T cell effector differentiation. In this study, we hypothesized tumor could be maintained aging through caloric restriction (CR) or dietary supplementation with resveratrol (RES), CR mimetic. Mice were placed on either...
Leflunomide is a novel immunomodulatory drug prescribed for treating rheumatoid arthritis.It inhibits the activity of protein tyrosine kinases and dihydroorotate dehydrogenase, rate-limiting enzyme in pyrimidine nucleotide synthesis pathway.Here, we report that A77 1726, active metabolite leflunomide, inhibited phosphorylation ribosomal S6 two other substrates S6K1, insulin receptor substrate-1 carbamoyl phosphate synthetase 2, an A375 melanoma cell line.A77 1726 increased AKT, p70 (S6K1),...
In patients with malignancy, the major barrier to achieving complete response is emergence of resistance current chemotherapeutic agents. One mechanisms by which tumour cells become resistant therapies altering cellular drug targets through mutations and/or deletions. Resistance this mechanism achieved more easily if has limited processes. We hypothesized that as Pseudomonas aeruginosa exotoxin T (ExoT) six proteins are required for cancer cell survival and proliferation, it highly unlikely...
Osteosarcoma patients often experience poor outcomes despite chemotherapy treatment, likely due in part to various mechanisms of tumor cell innate and/or acquired drug resistance. Exosomes, microvesicles secreted by cells, have been shown play a role resistance, but comprehensive protein signature relating osteosarcoma carboplatin resistance has not fully characterized.In this study, lysates and exosomes from two derivatives (HMPOS-2.5R HMPOS-10R) the HMPOS line generated repeated treatment...
A review of the literature finds that women diagnosed with breast cancer, who were on an aspirin regimen, experienced a decreased risk distant metastases and death. Several recent studies have reported improvement in overall survival colorectal cancer patients harbored mutations oncogene PIK3CA received daily regimen. Breast regimen is most frequently mutated occurring up to 45 % all cancers. In order determine if sensitized cancers treatment, we employed use isogenic cellular clones...
Abstract The requirements for circumventing tolerance induction in favor of memory T cell development are poorly understood. Although two signals (Ag and costimulation) necessary to drive effective clonal expansion, few cells remain after the response wanes. adjuvant LPS can increase numbers long-lived Ag-specific cells, but its mechanism action is not In this report, it shown that LPS, when combined with two-signal stimulation, profoundly enhances survival vivo. This does appear be...
OX40 engagement on activated T cells leads to increased proliferation, expansion and survival of Ag-specific cells. Direct ex vivo examination Ag-stimulated murine show that the Myc antagonists, Mxd4 Mnt, are transiently upregulated translocated nucleus following may be involved in suppressing cell death. Both Mnt stimulation through protein stability we identify a critical phosphorylation site controls stability. The upregulation contributes OX40-mediated T-cell because siRNA knockdown led...