A5087094854- Cancer Immunotherapy and Biomarkers
- Immune cells in cancer
- Immunotherapy and Immune Responses
- Extracellular vesicles in disease
- Immune Cell Function and Interaction
- RNA Interference and Gene Delivery
- Peptidase Inhibition and Analysis
- Nanoparticle-Based Drug Delivery
- Inflammation biomarkers and pathways
- Ferroptosis and cancer prognosis
- Cancer, Lipids, and Metabolism
- Inflammasome and immune disorders
- Nanoplatforms for cancer theranostics
- Circular RNAs in diseases
- Inflammatory Biomarkers in Disease Prognosis
- Adenosine and Purinergic Signaling
- MicroRNA in disease regulation
- interferon and immune responses
- Advanced Glycation End Products research
- Angiogenesis and VEGF in Cancer
- Adipokines, Inflammation, and Metabolic Diseases
- Lymphatic System and Diseases
- Bladder and Urothelial Cancer Treatments
- Neutropenia and Cancer Infections
- Chronic Myeloid Leukemia Treatments
Duke Medical Center
2019-2025
Duke University
2021-2024
Northwestern University
2013-2020
Midwestern University
2015-2020
Duke Cancer Institute
2019
Center for Cancer Research
2009
Purdue University West Lafayette
2009
Metastatic cancers produce exosomes that condition pre-metastatic niches in remote microenvironments to favor metastasis. In contrast, here we show from poorly metastatic melanoma cells can potently inhibit metastasis the lung. These "non-metastatic" stimulate an innate immune response through expansion of Ly6C
An in-depth understanding of immune escape mechanisms in cancer is likely to lead innovative advances immunotherapeutic strategies. However, much remains unknown regarding these and how they impact immunotherapy resistance. Using several preclinical tumor models as well clinical specimens, we identified a mechanism whereby CD8+ T cell activation response programmed death 1 (PD-1) blockade induced ligand 1/NOD-, LRR-, pyrin domain-containing protein 3 (PD-L1/NLRP3) inflammasome signaling...
Conventional dendritic cells (DCs) are essential mediators of antitumor immunity. As a result, cancers have developed poorly understood mechanisms to render DCs dysfunctional within the tumor microenvironment (TME). After identification CD63 as specific surface marker, we demonstrate that mature regulatory (mregDCs) migrate tumor-draining lymph node tissues and suppress DC antigen cross-presentation in trans while promoting T helper 2 cell differentiation. Transcriptional metabolic studies...
While immune checkpoint blockade is associated with prolonged responses in multiple cancers, most patients still do not benefit from this therapeutic strategy. The Wnt-β-catenin pathway diminished T cell infiltration; however, activating mutations are rare, implicating a role for autocrine/paracrine Wnt ligand-driven signaling evasion. In study, we show that proximal mediators of the anti-PD-1 resistance, and pharmacologic inhibition ligand supports efficacy by reversing dendritic...
Abstract Exosomes are nanoscale vesicles that mediate intercellular communication. Cellular exosome uptake mechanisms not well defined partly due to the lack of specific inhibitors this complex cellular process. Exosome depends on cholesterol-rich membrane microdomains called lipid rafts and can be blocked by non-specific depletion plasma cholesterol. Scavenger receptor type B-1 (SR-B1), found in rafts, is a for high-density lipoproteins (HDL). We hypothesized synthetic nanoparticle mimic...
Abstract Myeloid-derived suppressor cells (MDSC) are innate immune that potently inhibit T cells. In cancer, novel therapies aimed to activate can be rendered ineffective due the activity of MDSCs. Thus, targeted inhibition MDSCs may greatly enhance T-cell–mediated antitumor immunity, but mechanisms remain obscure. Here we show, for first time, scavenger receptor type B-1 (SCARB1), a high-affinity spherical high-density lipoprotein (HDL), is expressed by Furthermore, demonstrate SCARB1...
Primary tumours can establish long-range communication with distant organs to transform them into fertile soil for circulating tumour cells implant and proliferate, a process called pre-metastatic niche (PMN) formation. Tumour-derived extracellular vesicles (EV) are potent mediators of PMN formation due their diverse complement pro-malignant molecular cargo propensity target specific cell types (Costa-Silva et al., 2015; Hoshino Peinado 2012; 2017). While significant progress has been made...
The tumor-intrinsic NOD-, LRR- and pyrin domain-containing protein-3 (NLRP3) inflammasome–heat shock protein 70 (HSP70) signaling axis is triggered by CD8 + T cell cytotoxicity contributes to the development of adaptive resistance anti–programmed death 1 (PD-1) immunotherapy recruiting granulocytic polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) into tumor microenvironment. Here, we demonstrate that NLRP3-HSP70 also drives accumulation PMN-MDSCs distant lung tissues in a...
Efficient systemic administration of therapeutic short interfering RNA (siRNA) is challenging. High‐density lipoproteins (HDLs) are natural in vivo delivery vehicles. Specifically, native HDLs: 1) load single‐stranded RNA; 2) anionic, which requires charge reconciliation between the and HDL, 3) actively target scavenger receptor type B‐1 (SR‐B1) to deliver RNA. Emphasizing these particular parameters, templated lipoprotein particles (TLP), mimics spherical HDLs, employed self‐assembled with...
We have previously demonstrated that apigenin promotes the expression of antiangiogenic protein thrombospondin-1 (TSP1) via a mechanism driven by mRNA-binding HuR. Here, we generated novel mouse model with whole-body THBS-1 gene knockout on SKH-1 genetic background, which allows studies UVB-induced acute skin damage and carcinogenesis tests TSP1 involvement in apigenin's anticancer effects. Apigenin significantly inhibited wild-type (WT) animals but not KO (TKO) mice, suggesting is critical...
Abstract Therapeutic resistance to immune checkpoint blockade has been commonly linked the process of mesenchymal transformation (MT) and remains a prevalent obstacle across many cancer types. An improved mechanistic understanding for MT-mediated evasion promises lead more effective combination therapeutic regimens. Herein, we identified Hedgehog transcription factor, GLI2, as key node tumor-mediated immunotherapy during MT. GLI2 generated an immunotolerant tumor microenvironment through...
Abstract Previous studies have demonstrated dendritic cell (DC)-mediated T activation to be impaired within the tumor microenvironment (TME). This has included showing that of XBP1 unfolded protein response (UPR) pathway triggers lipid accumulation by DCs TME, however signal mediating remained unclear. We previously fatty acid oxidation (FAO) as well SREBP2-dependent mevalonate biosynthetic leads development mregDCs in exhibiting antigen cross-presentation and an enhanced capacity drive...
<div>Abstract<p>Therapeutic resistance to immune checkpoint blockade has been commonly linked the process of mesenchymal transformation (MT) and remains a prevalent obstacle across many cancer types. An improved mechanistic understanding for MT-mediated evasion promises lead more effective combination therapeutic regimens. Herein, we identified hedgehog transcription factor, GLI2, as key node tumor-mediated immunotherapy during MT. GLI2 generated an immunotolerant tumor...
<p>Supplementary Figures and Tables</p>
Abstract Exosomes are produced by cells to mediate intercellular communication and have been shown perpetuate diseases, including cancer. New tools needed understand exosome biology, detect exosomes from specific cell types in complex biological media modify exosomes. Our data demonstrate a cellular pathway whereby membrane-bound scavenger receptor type B-1 (SR-B1) parent becomes incorporated into We tailored synthetic HDL-like nanoparticles (HDL NP), high-affinity ligands for SR-B1, carry...
Dendritic cells (cDCs) are essential mediators of anti-tumor immunity. Cancers have developed mechanisms to render DCs dysfunctional within the tumor microenvironment. Utilizing CD63 as a unique surface marker, we demonstrate that mature regulatory (mregDCs) suppress DC antigen cross-presentation while driving T H 2 and cell differentiation tumor-draining lymph node tissues. Transcriptional metabolic studies show mregDC functionality is dependent upon mevalonate biosynthetic pathway master...
Abstract Therapeutic resistance to immune checkpoint blockade has been commonly linked the process of mesenchymal transformation (MT) and remains a prevalent obstacle across many cancer types. An improved mechanistic understanding for MT-mediated evasion promises lead more effective combination therapeutic regimens. Herein, we identify Hedgehog transcription factor, Gli2, as key node tumor-mediated immunotherapy during MT. Mechanistic studies reveal that Gli2 generates an immunotolerant...
<h3>Background</h3> Efforts to enhance the efficacy of anti-PD-1 immunotherapy has resulted in only modest improvements clinical responses several solid tumor patient populations. An improved understanding tumor-mediated immune evasion mechanisms is needed identify novel pharmacologic targets for sensitizing traditionally refractory types checkpoint inhibitor immunotherapy. We have previously demonstrated that tumor-intrinsic NLRP3 inflammasome supports and resistance by promoting...