A5018650939- Immune Cell Function and Interaction
- CAR-T cell therapy research
- RNA modifications and cancer
- Immunotherapy and Immune Responses
- Epigenetics and DNA Methylation
- Cancer Immunotherapy and Biomarkers
- Cancer, Hypoxia, and Metabolism
- Cancer-related gene regulation
- Cancer Research and Treatments
- Virus-based gene therapy research
- Monoclonal and Polyclonal Antibodies Research
- Immune cells in cancer
- Biochemical and Molecular Research
- RNA and protein synthesis mechanisms
- Mycobacterium research and diagnosis
- RNA Research and Splicing
- PI3K/AKT/mTOR signaling in cancer
- RNA Interference and Gene Delivery
- Cancer Cells and Metastasis
- MicroRNA in disease regulation
- Metabolism, Diabetes, and Cancer
- Glycosylation and Glycoproteins Research
- Cancer-related molecular mechanisms research
- Ubiquitin and proteasome pathways
- Peptidase Inhibition and Analysis
The University of Texas MD Anderson Cancer Center
2014-2023
China Medical University
2013-2023
China Medical University Hospital
2009-2023
Cellular Research (United States)
2023
University of South Dakota
2013-2023
Avera Health
2023
Sanford USD Medical Center
2022
Comprehensive Cancer Center Vienna
2021
Medical University of Vienna
2021
Anzac Research Institute
2016-2020
Abstract Extracellular interaction between programmed death ligand-1 (PD-L1) and cell protein-1 (PD-1) leads to tumour-associated immune escape. Here we show that the immunosuppression activity of PD-L1 is stringently modulated by ubiquitination N -glycosylation. We glycogen synthase kinase 3β (GSK3β) interacts with induces phosphorylation-dependent proteasome degradation β-TrCP. In-depth analysis N192, N200 N219 glycosylation suggests antagonizes GSK3β binding. In this regard, only...
Purpose: To explore whether a cross-talk exists between PARP inhibition and PD-L1/PD-1 immune checkpoint axis, determine blockade of potentiates inhibitor (PARPi) in tumor suppression.Experimental Design: Breast cancer cell lines, xenograft tumors, syngeneic tumors treated with PARPi were assessed for PD-L1 expression by immunoblotting, IHC, FACS analyses. The phospho-kinase antibody array screen was used to the underlying mechanism PARPi-induced upregulation. therapeutic efficacy alone, or...
Abstract Proinflammatory cytokines produced in the tumor microenvironment facilitate development and metastatic progression. In particular, TNF-α promotes cancer invasion angiogenesis associated with epithelial–mesenchymal transition (EMT); however, mechanisms underlying its induction of EMT cells remain unclear. Here we show that stemness properties induced by chronic treatment are mediated upregulation transcriptional repressor Twist1. Exposure to rapidly Twist1 mRNA protein expression...
The two T cell inhibitory receptors PD-1 and TIM-3 are co-expressed during exhausted differentiation, recent evidence suggests that their crosstalk regulates exhaustion immunotherapy efficacy; however, the molecular mechanism is unclear. Here we show contributes to persistence of
Enriched PD-L1 expression in cancer stem-like cells (CSCs) contributes to CSC immune evasion. However, the mechanisms underlying enrichment CSCs remain unclear. Here, we demonstrate that epithelial-mesenchymal transition (EMT) enriches by EMT/β-catenin/STT3/PD-L1 signaling axis, which EMT transcriptionally induces N-glycosyltransferase STT3 through β-catenin, and subsequent STT3-dependent N-glycosylation stabilizes upregulates PD-L1. The axis is also utilized general cell population, but it...
In the tumour microenvironment, critical drivers of immune escape include oncogenic activity cell-intrinsic osteopontin (OPN), expression programmed death ligand 1 (PD-L1) and expansion tumour-associated macrophages (TAMs). We investigated feasibility targeting these pathways as a therapeutic option in hepatocellular carcinoma (HCC) mouse models.We analysed number tumour-infiltrating cells inflammatory profiles chemically induced liver isolated from wild-type OPNknockout (KO) mice. vitro...
Glycosylation of immune receptors and ligands, such as T cell receptor coinhibitory molecules, regulates signaling activation surveillance. However, how oncogenic initiates glycosylation molecules to induce immunosuppression remains unclear. Here we show that IL-6-activated JAK1 phosphorylates programmed death-ligand 1 (PD-L1) Tyr112, which recruits the endoplasmic reticulum-associated N-glycosyltransferase STT3A catalyze PD-L1 maintain stability. Targeting IL-6 by antibody induced...
Immune checkpoint blockade therapy has demonstrated promising clinical outcomes for multiple cancer types. However, the emergence of resistance as well inadequate biomarkers patient stratification have largely limited benefits. Here, we showed that tumors with high TYRO3 expression exhibited anti–programmed cell death protein 1/programmed ligand 1 (anti–PD-1/PD-L1) in a syngeneic mouse model and patients who received anti–PD-1/PD-L1 therapy. Mechanistically, inhibited tumor ferroptosis...
Oncogenic signaling reprograms cancer cell metabolism to augment the production of glycolytic metabolites in favor tumor growth. The ability cells evade immunosurveillance and role metabolic regulators T-cell functions suggest that oncogene-induced reprogramming may be linked immune escape. EGF signaling, frequently dysregulated triple-negative breast (TNBC), is also associated with increased glycolysis. Here, we demonstrated TNBC activates first step glycolysis, but impedes last step,...
Immunotherapies targeting programmed cell death protein 1 (PD-1) and ligand (PD-L1) immune checkpoints represent a major breakthrough in cancer treatment. PD-1 is an inhibitory receptor expressed on the surface of activated T cells that dampens T-cell (TCR)/CD28 signaling by engaging with its PD-L1 cells. Despite clinical success blockade using mAbs, most patients do not respond to treatment, underlying regulatory mechanisms remain incompletely defined. Here we show extensively...
Colorectal cancer is the second leading cause of death from in United States. Metastases liver, most common metastatic site for colorectal cancer, are found one-third patients who die cancer. Currently, genes and molecular mechanisms that functionally critical modulating hepatic metastasis remain unclear. Here, we report our studies using functional selection an orthotopic mouse model to identify a set play important role mediating liver metastasis. These included APOBEC3G, CD133, LIPC,...
Abstract Purpose: Results of multiple clinical trials suggest that EGF receptor (EGFR) tyrosine kinase inhibitors (TKI) exhibit negative effects on platinum-based chemotherapy in patients with lung cancer wild-type (WT) EGFR, but the underlying molecular mechanisms are still uncertain. Studies identify mechanism how TKIs negatively affect WT EGFR important for future development effective strategies to target cancer. Thus, we returned vitro study investigate and determine a possible...
The first-in-human clinical trial with human bolus intravenous infusion IL15 (rhIL15) was limited by treatment-associated toxicity. Here, we report toxicity, immunomodulation, and activity of rhIL15 administered as a 10-day continuous (CIV) to patients cancers in phase I trial.Patients received treatment for 10 days CIV doses 0.125, 0.25, 0.5, 1, 2, or 4 μg/kg/day. Correlative laboratory tests included pharmacokinetic (PK) analyses, assessment changes lymphocyte subset numbers.Twenty-seven...
Abstract Triple-negative breast cancer (TNBC), which lacks estrogen receptor α (ERα), progesterone receptor, and human epidermal growth factor 2 (HER2) expression, is closely related to basal-like cancer. Previously, we others report that cyclin E/cyclin-dependent kinase (CDK2) phosphorylates enhancer of zeste homolog (EZH2) at T416 (pT416-EZH2). Here, show transgenic expression phospho-mimicking EZH2 mutant T416D in mammary glands leads tumors with TNBC phenotype. Coexpression epithelia...