A5080552007- Bone health and treatments
- Cancer Research and Treatments
- Pancreatic and Hepatic Oncology Research
- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Cancer Cells and Metastasis
- T-cell and B-cell Immunology
- Biochemical and Molecular Research
- Immune cells in cancer
- Inflammatory mediators and NSAID effects
- Ferroptosis and cancer prognosis
- Chemokine receptors and signaling
- Phagocytosis and Immune Regulation
- Monoclonal and Polyclonal Antibodies Research
- Cancer-related Molecular Pathways
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Single-cell and spatial transcriptomics
- RNA Interference and Gene Delivery
- Cancer, Lipids, and Metabolism
- Immune responses and vaccinations
- Cancer, Hypoxia, and Metabolism
- Peptidase Inhibition and Analysis
University of Pennsylvania
2020-2025
Seoul National University
2010-2025
UPMC Hillman Cancer Center
2020-2024
Cancer Research Institute
2020-2024
California University of Pennsylvania
2023
Namseoul University
2017
St. Vincent's Hospital
2015
Catholic University of Korea
2014
Pukyong National University
2010
Abstract Mutations in the KRAS oncogene are found more than 90% of patients with pancreatic ductal adenocarcinoma (PDAC), Gly-to-Asp mutations (KRASG12D) being most common. Here, we tested efficacy a small-molecule KRASG12D inhibitor, MRTX1133, implantable and autochthonous PDAC models an intact immune system. In vitro studies validated specificity potency MRTX1133. vivo, MRTX1133 prompted deep tumor regressions all tested, including complete or near-complete remissions after 14 days....
Abstract During cancer immunoediting, loss of major histocompatibility complex class I (MHC-I) in neoplasm contributes to the evasion tumours from host immune system. Recent studies have demonstrated that most natural killer (NK) cells are found advanced cancers defective, releasing malignant MHC-I-deficient NK-cell-dependent control. Here, we show a T (NKT)-cell-ligand-loaded tumour-antigen expressing antigen-presenting cell (APC)-based vaccine effectively eradicates these tumours. this...
Abstract Although immunotherapy has revolutionized cancer care, patients with pancreatic ductal adenocarcinoma (PDA) rarely respond to these treatments, a failure that is attributed poor infiltration and activation of T cells in the tumor microenvironment (TME). We performed an vivo CRISPR screen identified lysine demethylase 3A (KDM3A) as potent epigenetic regulator response PDA. Mechanistically, KDM3A acts through Krueppel-like factor 5 (KLF5) SMAD family member 4 (SMAD4) regulate...
Summary Aging is accompanied by altered T‐cell responses that result in susceptibility to various diseases. Previous findings on the increased expression of inhibitory receptors, such as programmed cell death protein 1 ( PD ‐1), T cells aged mice emphasize importance investigations into relationship between exhaustion and aging‐associated immune dysfunction. In this study, we demonstrate immunoglobulin mucin domain‐3 (Tim‐3), another marker, up‐regulated cells, especially CD 8 + cells....
Acquired resistance to immunotherapy remains a critical yet incompletely understood biological mechanism. Here, using mouse model of pancreatic ductal adenocarcinoma (PDAC) study tumor relapse following immunotherapy-induced responses, we find that is reproducibly associated with an epithelial-to-mesenchymal transition (EMT), EMT-transcription factors ZEB1 and SNAIL functioning as master genetic epigenetic regulators this effect. in not due immunosuppression the immune microenvironment,...
Abstract Activating mutations in KRAS drive tumorigenesis pancreatic ductal adenocarcinoma (PDAC), promoting tumor cell proliferation and contributing to an immunosuppressive microenvironment (TME) rendering PDAC tumors insensitive immunotherapy. RAS(ON) multi-selective inhibitors, such as daraxonrasib (RMC-6236) RMC-7977, target the active state of RAS, with potent anti-tumor activity murine models. Here, we report that inhibition led rapid profound regressions immunocompetent mice,...
Genetic and epigenetic programming of T helper (Th) cell subsets during their polarization from naive Th cells establishes long-lived memory that stably maintain lineage signatures. However, whether can be redifferentiated into another is unclear. In this study, we show Ag-specific were Foxp3 + by TGF-β when stimulated in the presence all-trans retinoic acid rapamycin. The “converted” derived Th2 down-regulated GATA-3 IRF4 produced little IL-4, IL-5, IL-13. Instead, converted suppressed...
Abstract PD-1–based cancer immunotherapy is a successful example of immune checkpoint blockade that provides long-term durable therapeutic effects in patients with across wide spectrum types. Accumulating evidence suggests anti-PD-1 therapy enhances antitumor immunity by reversing the function exhausted T cells tumor environment. However, responsiveness rate to remains low, providing an urgent need for optimization and improvement. In this study, we designed anti-PD-1–resistant mouse model...
Abstract Pancreatic cancer metastasis is a leading cause of cancer-related deaths, yet very little understood regarding the underlying biology. As result, targeted therapies to inhibit are lacking. Here, we report that parathyroid hormone–related protein (PTHrP encoded by PTHLH) frequently amplified as part KRAS amplicon in patients with pancreatic cancer. PTHrP upregulation drives growth both primary and metastatic tumors mice highly enriched ductal adenocarcinoma metastases. Loss...
Oncogenesis and progression of pancreatic ductal adenocarcinoma (PDAC) are driven by complex interactions between the neoplastic component tumor microenvironment, which includes immune, stromal, parenchymal cells. In particular, most PDACs characterized a hypovascular hypoxic environment that alters cell behavior limits efficacy chemotherapy immunotherapy. Characterization spatial features vascular niche could advance our understanding inter- intratumoral heterogeneity in PDAC. this study,...
Monocyte-derived dendritic cells (moDCs) have been shown to robustly expand during infection; however, their roles in anti-infectious immunity remain unclear. Here, we found that moDCs were dramatically increased the secondary lymphoid organs acute LCMV infection an interferon-γ (IFN-γ)-dependent manner. We also priming by enhanced differentiation of memory CD8+ T compared primed conventional (cDCs) through upregulation Eomesodermin (Eomes) and cell factor-1 (TCF-1) expression cells....
<p>Supplementary Figures</p>
<div>Abstract<p>PD-1–based cancer immunotherapy is a successful example of immune checkpoint blockade that provides long-term durable therapeutic effects in patients with across wide spectrum types. Accumulating evidence suggests anti-PD-1 therapy enhances antitumor immunity by reversing the function exhausted T cells tumor environment. However, responsiveness rate to remains low, providing an urgent need for optimization and improvement. In this study, we designed...
Abstract Activating mutations in KRAS drive tumorigenesis more than 90% of cases pancreatic ductal adenocarcinoma (PDAC), promoting tumor cell proliferation and survival contributing to an immunosuppressive microenvironment (TME). RAS(ON) multi-selective inhibitors, such as RMC-6236 RMC-7977, potently block the active state mutant wild-type RAS isoforms show profound anti-tumor activity PDAC murine models1. Here, we utilized a panel immunocompetent mouse models evaluate extent which adaptive...
Abstract Lymph nodes (LNs) are the staging grounds for anti-tumor immunity, therefore their high susceptibility to metastatic colonization is a paradox. Previous studies have suggested that extrinsic tumor-derived factors precondition draining LN enable tumor cell survival by promoting state of immune suppression. Here, we investigate whether properties itself may impede its ability clear metastasizing cells. Using multiple immunocompetent transplant models, show LNs possess intrinsic...
GM-CSF as an adjuvant has been shown to promote antitumor immunity in mice and humans; however, the underlying mechanism of GM-CSF-induced remains incompletely understood. In this study, we demonstrate that potentiates efficacy cancer vaccines through IL9-producing Th (Th9) cells. selectively enhanced Th9 cell differentiation by regulating COX2-PGE2 pathway while inhibiting induced regulatory T (iTreg) cells vitro vivo GM-CSF-activated monocyte-derived dendritic converted tumor-specific...
The generation of antigen-specific cytotoxic T lymphocyte (CTL) responses is required for successful cancer vaccine therapy. In this regard, ligands Toll-like receptors (TLRs) have been suggested to activate adaptive immune by modulating the function antigen-presenting cells (APCs). Despite their therapeutic potential, development TLR immunotherapy often hampered due rapid systemic toxicity. Regarding safety concerns currently available ligands, finding a new agonist with potent efficacy and...
Tumor cell-derived prostaglandin E2 (PGE2) is a tumor cell-intrinsic factor that supports immunosuppression in the microenvironment (TME) by acting on immune cells, but impact of PGE2 signaling cells immunosuppressive TME unclear. We demonstrate deleting synthesis enzyme or disrupting autocrine through EP4 receptors reverses T cell-low, myeloid cell-rich TME, activates and suppresses growth. Knockout (KO) Ptges (the gene encoding mPGES-1) receptor (Ptger4) KPCY (KrasG12D/P53R172H/Yfp/CrePdx)...
Although treatment with the glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) agonistic antibody (DTA-1) has shown antitumor activity in various models, underlying mechanism is not fully understood. Here, we demonstrate that interleukin (IL)-21-producing follicular helper T (Tfh) cells play a crucial role DTA-1-induced inhibition. The administration of DTA-1 increased IL21 expression by Tfh an antigen-specific manner, and this activation led to enhanced cytotoxic...
Human infection caused by Shewanella algae is rare, which usually occurred after direct contact with seawater or ingestion of raw seafood in the immunocompromised host. There have been anecdotal reports about infections human, but their pathogenic role and microbiologic data are limited. Here, we report a fatal case spontaneous bacterial peritonitis bacteremia due to S. 57-year-old male liver cirrhosis who had no history exposure seafood. Polymicrobial Streptococcus mitis Escherichia coli...