A5039261944- Immune Cell Function and Interaction
- Nitric Oxide and Endothelin Effects
- Immune cells in cancer
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Cancer, Stress, Anesthesia, and Immune Response
- Inflammatory mediators and NSAID effects
- Cancer Immunotherapy and Biomarkers
- Hydrogen's biological and therapeutic effects
- Chemokine receptors and signaling
- Cytokine Signaling Pathways and Interactions
- Cancer Research and Treatments
- IL-33, ST2, and ILC Pathways
- Inflammatory Biomarkers in Disease Prognosis
- Inflammasome and immune disorders
- Eicosanoids and Hypertension Pharmacology
- Inflammation biomarkers and pathways
- Pancreatic function and diabetes
- Renal and related cancers
- Hair Growth and Disorders
- Systemic Lupus Erythematosus Research
- RNA modifications and cancer
- Reproductive System and Pregnancy
- Neuroinflammation and Neurodegeneration Mechanisms
- Single-cell and spatial transcriptomics
Center for Cancer Research
2007-2025
National Cancer Institute
2009-2025
National Institutes of Health
1995-2015
Cancer Institute (WIA)
2003-2015
Albany Medical Center Hospital
2012
Frederick Community College
2010
Frederick National Laboratory for Cancer Research
2001-2005
Data Management Services (United States)
2002
Abstract TNFR2 is predominantly expressed by a subset of human and mouse CD4+CD25+FoxP3+ T regulatory cells (Tregs). In this study, we characterized the phenotype function TNFR2+ Tregs in peripheral lymphoid tissues normal tumor-bearing C57BL/6 mice. We found that was on 30–40% activated/memory were most highly suppressive. contrast, TNFR2− exhibited naive only had minimal suppressive activity. Although not typically considered to be Tregs, CD4+CD25−TNFR2+ nevertheless possessed moderate...
Neutrophils are a vital component of immune protection, yet in cancer they may promote tumour progression, partly by generating reactive oxygen species (ROS) that disrupts lymphocyte functions. Metabolically, neutrophils often discounted as purely glycolytic. Here we show immature, c-Kit+ subsets can engage oxidative mitochondrial metabolism. With limited glucose supply, use fatty acid oxidation to support NADPH oxidase-dependent ROS production. In 4T1 tumour-bearing mice, fitness is...
Previously, we found that co-expression of CD25 and TNFR2 identified the most suppressive subset mouse Treg. In this study, report human peripheral blood (PB) FOXP3(+) cells present in CD25(high), CD25(low) even CD25(-) subsets CD4(+) expressed high levels TNFR2. Consequently, TNFR2-expressing CD4(+)CD25(+) Treg included all CD4(+)CD25(high) as well a substantial proportion CD4(+)CD25(low) subset. Flow cytometric analysis PB five-fold more Treg, determined by FOXP3 expression,...
Abstract Our previous study showed that TNFR2 is preferentially expressed by CD4+FoxP3+ regulatory T cells (Tregs), and expression of this receptor identified maximally suppressive Tregs. also a small fraction CD4+FoxP3− conventional (Tconvs) in normal mice, its upregulated cell activation. This raises questions about the role signaling function Tconv cells. In study, using FoxP3/gfp knock-in we did not induce FoxP3− CD4 to become suppressive. Ki-67, marker proliferation, was concomitantly...
MIF is a proinflammatory cytokine and implicated in cancer. A higher level found many human cancer cancer-prone inflammatory diseases, including chronic pancreatitis pancreatic We tested the hypothesis that contributes to aggressiveness predicts disease outcome resected cases. Consistent with our we an elevated mRNA expression tumors was significantly associated poor Multivariate Cox-regression analysis further showed independently patients' survival (HR = 2.26, 95% CI 1.17-4.37, p 0.015)....
Abstract IL-7 is vital for the development of immune system and profoundly enhances function mature T cells. Chronic administration to mice markedly increases cell numbers, especially CD8+ cells, functional potential. However, mechanism by which these effects occur remains unclear. This report demonstrates that only 2 days treatment needed maximal enhancement function, as measured proliferation, with a 6- 12-fold increase in proportion CD4+ cells cycle 18 h ex vivo stimulation. Moreover,...
Abstract Inflammation influences the development of cancer. The nitric oxide synthase (NOS2) is induced by inflammatory cytokines, e.g., tumor necrosis factor α and interleukin 1β, produces (NO·), a critical mediator response. Because p53 governs NO· production transcriptionally transrepressing NOS2, we used genetic strategy to determine whether cooperatively regulate tumorigenesis. Lymphomas developed more rapidly in p53−/−NOS2−/− or p53−/−NOS2+/− mice than p53−/−NOS2+/+ that were...
Nitric oxide (NO(*)), an important signaling molecule and a component of inflammatory response, is involved in tumorigenesis. However, the quantity NO(*) cellular microenvironment influences role tumor development. We used genetic strategy to test hypothesis that with enhanced level accelerates spontaneous C. parvum-induced inflammation increased synthase-2 (NOS2) expression coincided accelerated development, mostly lymphomas, p53-/-NOS2+/+ C57BL6 mice when compared controls (P = 0.001)....
Systemic administration of IL-12 and intermittent doses IL-2 induce complete regression metastatic murine renal carcinoma. Here, we show that overt tumor induced by IL-12/pulse is preceded recruitment CD8+ T cells, vascular injury, disrupted neovascularization, apoptosis both endothelial cells. The IL-12/IL-2 combination synergistically enhances cell surface FasL expression on lymphocytes in vitro induces Fas within tumors via an IFN-γ–dependent mechanism vivo. This therapy also inhibits...
The carefully orchestrated events that result in a protective immune response are coordinated to large extent by cytokines produced T helper 1 (Th1) and 2 (Th2) T-cell subsets, which two arms of the system. Th1 cells preferentially produce interleukin (IL-2), interferon gamma (IFN gamma), tumor necrosis factor (TNF), resulting cellular helps eliminate infected cells. In contrast, Th2 IL-4, IL-5, IL-6, IL-10 stimulate an antibody prevent from becoming infected. clinical progression several...
Systemic administration of IL-12 and intermittent doses IL-2 induce complete regression metastatic murine renal carcinoma. Here, we show that overt tumor induced by IL-12/pulse is preceded recruitment CD8+ T cells, vascular injury, disrupted neovascularization, apoptosis both endothelial cells. The IL-12/IL-2 combination synergistically enhances cell surface FasL expression on lymphocytes in vitro induces Fas within tumors via an IFN-γ–dependent mechanism vivo. This therapy also inhibits...
Abstract Fas ligand expression in certain tumors has been proposed to contribute immunosuppression and poor prognosis. However, immunotherapeutic approaches may elicit the Fas-mediated elimination of immunosuppressive regulatory T cells (Tregs) myeloid-derived suppressor (MDSCs) within that represent major obstacles for cancer immunotherapy. Previously, we showed IL-2 agonistic CD40 Ab (αCD40) elicited synergistic antitumor responses coincident with efficient removal Tregs MDSCs. We...
Myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAM) contribute to cancer-related inflammation tumor progression. While several myeloid molecules have been ascribed a regulatory function in these processes, the triggering receptors expressed on (TREMs) emerged as potent modulators of innate immune response. various TREMs amplify inflammation, others dampen it are emerging important players modulating progression—for instance, soluble TREM-1 (sTREM-1), which is...
The human T-cell leukemia type-1 (HTLV-1) retrovirus establishes chronic life-long infection in a fraction of infected individuals associated with severe pathological conditions. Although the mechanism driving disease development is not fully understood, current evidence indicates essential functions viral regulatory proteins. Among these, p13 protein has previously been shown to localize inner mitochondrial membrane T cells, altering biology and function. While CD4+ cells are primary cell...
Skin keratinocytes are major mediators of host immune responses. The skin is also a target for immunologically based inflammation in many pathological states. Activation protein kinase C (PKC) can induce cutaneous inflammation, but the precise role each six PKC isoforms (alpha, delta, epsilon, eta, zeta, mu) that regulate normal homeostasis or contribute to pathology has not been clarified. We generated transgenic mice overexpress PKCalpha basal layer epidermis and outer root sheath hair...
Abstract IFN-γ is a critical component of the endogenous and many cytokine-induced antitumor immune responses. In this study we have shown that combination IL-18 IL-2 (IL-18/IL-2) synergistically enhances production both in vitro vivo, synergizes vivo to induce complete durable regression well-established 3LL tumors >80% treated mice. We observed nascent, but ineffective, host response against depends on IL-12 Fas/Fas ligand (Fas-L) pathway. The combined administration IL-18/IL-2...
Natural Killer (NK) cells have an important role in immune responses to viruses and tumours. Integrating changes signal transduction pathways cellular metabolism is essential for effective NK responses. The glycolytic enzyme Pyruvate Kinase Muscle 2 (PKM2) has described roles regulating flux transduction, particularly gene transcription. While PKM2 expression robustly induced activated cells, mice lacking showed no defect cell metabolism, transcription or antiviral MCMV infection. was...
The HLA-C gene appears to have evolved in higher primates serve as a dominant source of ligands for the KIR2D family inhibitory MHC class I receptors. expression NK cell-intrinsic has been shown regulate murine Ly49 receptors due interaction these with cell cis. However, cis interactions not demonstrated human KIR and HLA proteins. We report discovery an elaborate cell-specific system regulating expression, indicating important role development function cells. A large array alternative...
<h3>Objectives</h3> The relative contributions of inflammatory signalling and sequential oncogenic dysregulation driving liver cancer pathogenesis remain incompletely understood. Lymphotoxin-β receptor (LTβR) is critically involved in hepatitis tumorigenesis. Therefore, we explored the interdependence lymphotoxin specific pathways progression hepatic cancer. <h3>Design</h3> Pathologically distinct tumours were initiated by hydrodynamic transfection V-Akt Murine Thymoma Viral Oncogene Homolog...
Abstract The IFN-γ-inducible proteins monokine induced by IFN-γ (Mig) and chemokine responsive to γ-2 (Crg-2) can contribute IL-12-induced antiangiogenic leukocyte-recruiting activities, but the extent which leukocytes vs parenchymal cells in different organs production of these molecules remains unclear. results presented herein show that IFN-γ-dependent induction Mig Crg-2 gene expression occur many nonlymphoid organs, genes are rapidly purified hepatocytes isolated from mice treated with...
Abstract The fate of invariant NKT (iNKT) cells following activation remains controversial and unclear. We systemically examined how iNKT are regulated TCR-dependent -independent with α-galactosylceramide (αGC) or IL-18 plus IL-12, respectively. Our studies reveal by αGC IL-12 induced transient depletion exclusively in the liver that was independent caspase 3-mediated apoptosis. loss followed repopulation expansion phenotypically distinct via different mechanisms. Liver cell αGC, but not...