A5086417927- Protease and Inhibitor Mechanisms
- Immunotherapy and Immune Responses
- Immune cells in cancer
- Immune Cell Function and Interaction
- Cell Adhesion Molecules Research
- Chemokine receptors and signaling
- T-cell and B-cell Immunology
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Cancer, Stress, Anesthesia, and Immune Response
- Receptor Mechanisms and Signaling
- Monoclonal and Polyclonal Antibodies Research
- Inflammatory mediators and NSAID effects
- Galectins and Cancer Biology
- Immune Response and Inflammation
- Psoriasis: Treatment and Pathogenesis
- Nanoparticle-Based Drug Delivery
- S100 Proteins and Annexins
- Mesenchymal stem cell research
- interferon and immune responses
- Glycosylation and Glycoproteins Research
- Tryptophan and brain disorders
- Cancer Mechanisms and Therapy
- Tissue Engineering and Regenerative Medicine
- NF-κB Signaling Pathways
University of Pittsburgh
2011-2024
UPMC Hillman Cancer Center
2011-2023
Janssen (Belgium)
2019-2023
Johnson & Johnson (United States)
2019
Target (United States)
2019
Data Harbor (United States)
2015
University of Ljubljana
2006-2014
Jožef Stefan Institute
2009-2014
University of Regensburg
2013-2014
University Hospital Regensburg
2014
Abstract Signals mediated by CXCL12 (SDF1) and its receptor CXCR4 are centrally involved in cancer progression, both directly activating cells indirectly inducing angiogenesis plus recruiting T regulatory plasmacytoid dendritic immune cells. Here, we show that ascites isolated from ovarian patients, controlled the tumor-associated inflammatory mediator prostaglandin E2 (PGE2), which attracts myeloid-derived suppressor (MDSC) into microenvironment. In this setting, PGE2 was essential for...
The generation of effective type 1 T helper (Th1)-cell responses is required for immunity against intracellular bacteria. However, some bacteria require interleukin (IL)-17 to drive Th1-cell and subsequent protective host immunity. Here, in a model Mycobacterium bovis Bacille Calmette-Guerin (BCG) vaccination mice, we demonstrate that the dependence on IL-17 mechanism overcome bacteria-induced IL-10 inhibitory effects. We show BCG-induced prostaglandin-E2 (PGE2) promotes production which...
Abstract Th17 and regulatory T (T reg ) cells are integral in maintaining immune homeostasis Th17–T imbalance is associated with inflammatory immunosuppression cancer. Here we show that a source of tumour-induced Foxp3 + cells. In addition to natural (n)T induced (i)T develop from naive precursors, suppressive IL-17A ex-Th17 converted neg tumour-bearing mice. Metabolic phenotyping Foxp3-expressing , iT demonstrates the dissociation between metabolic fitness function cell subsets. Although...
The ultimate goal in transplantation medicine is the promotion of operational tolerance. Although Th cells Th17 type have been predominantly associated with rejection allogeneic solid organ grafts, regulatory T (T(reg)) appear to foster Induced T(reg) and a higher lineage plasticity than has recognized thus far. We found that when mesenchymal stem (MSCs) were used induce long-term acceptance heart grafts mice, induction was preceded by development CD11b(hi)Gr1(int) myeloid-derived...
Highlights•PGE2 induces specific upregulation of DNMT3A in MDSCs•MDSC-suppressive properties depend on and hypermethylation myeloid genes•Specific DNMT3A-mediated changes MDSCs suggest potential therapeutic targets•PGE2- DNMT3A-dependent effects occur vitro models primary samplesSummaryMyeloid-derived suppressor cells (MDSCs) dendritic (DCs) arise from common progenitors. Tumor-derived factors redirect differentiation immune-promoting DCs to tolerogenic MDSCs, an immunological hallmark...
Nitric oxide (NO) is a ubiquitous mediator of inflammation and immunity, involved in the pathogenesis control infectious diseases, autoimmunity, cancer. We observed that expression nitric synthase-2 (NOS2/iNOS) positively correlates with Th17 responses patients ovarian cancer (OvCa). Although high concentrations exogenous NO indiscriminately suppress proliferation differentiation Th1, Th2, cells, physiological produced by patients’ myeloid-derived suppressor cells (MDSCs) support development...
Resveratrol is a polyphenol that acts on multiple molecular targets important for cell differentiation and activation. Dendritic cells (DCs) are functionally diverse type represent the most potent antigen-presenting of immune system. In this study, we investigated resveratrol-induced effects DCs during their maturation. Our results show resveratrol induces DC-associated tolerance, particularly when applied DC differentiation. Costimulatory molecules CD40, CD80 CD86 were down-regulated, as...
Myeloid-derived suppressor cells (MDSCs) are natural immunosuppressive and endogenous inhibitors of the immune system. We describe a simple clinically compatible method generating large numbers MDSCs using cultures peripheral blood-isolated monocytes supplemented with prostaglandin E2 (PGE2). observed that PGE2 induces cyclooxygenase (COX)2 expression in cultured monocytes, blocking their differentiation into CD1a+ dendritic (DCs) inducing indoleamine 2,3-dioxygenase 1, IL-4Rα, nitric oxide...
γ-Enolase, a glycolytic enzyme, is expressed specifically in neurons. It exerts neurotrophic activity and has been suggested to regulate growth, differentiation, survival regeneration of In the present study, we investigated involvement γ-enolase PI3K (phosphoinositide 3-kinase)/Akt MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) signalling, two pathways triggered predominantly by factors. Whereas PI3K/Akt pathway, rather than MAPK/ERK involved...
A new trick for an old dog! Aberrant cathepsin B activity is associated with tumor progression, however, despite extensive research, there are no inhibitors in clinical use. Here, nitroxoline, established antimicrobial agent, identified as a potent, reversible inhibitor of B, and thus potential drug candidate the treatment cancer other diseases which plays role.
The Fourth Expert Meeting of the Mesenchymal Stem Cells in Solid Organ Transplantation (MiSOT) Consortium took place Barcelona on October 19 and 20, 2012. This meeting focused translation preclinical data into early clinical settings. position paper highlights main topics explored safety efficacy mesenchymal stem cells as a therapeutic agent solid organ transplantation emphasizes issues (proper timing, concomitant immunossupression, source immunogenicity cells, oncogenicity) that have been...
In Brief Background The human regulatory macrophage (Mreg) has emerged as a promising cell type for use cell-based adjunct immunosuppressive therapy in solid organ transplant recipients. this brief report, dehydrogenase/reductase 9 (DHRS9) is identified robust marker of Mregs. Methods cognate antigen mouse monoclonal antibody raised against Mregs was DHRS9 by immunoprecipitation and MALDI-MS sequencing. Expression within panel monocyte-derived macrophages investigated quantitative PCR,...
γ-Enolase is a neurotrophic-like factor promoting growth, differentiation, survival and regeneration of neurons. Its neurotrophic activity regulated by cysteine protease cathepsin X which cleaves the C-terminal end molecule. We have investigated expression colocalization γ-enolase in brains Tg2576 mice overexpressing amyloid precursor protein. In situ hybridization revealed that mRNAs for both enzymes were expressed abundantly around plaques. Immunostaining demonstrated C-terminally cleaved...
Abstract Maintenance of CTL-, Th1-, and NK cell–mediated type-1 immunity is essential for effective antitumor responses. Unexpectedly, we observed that the critical soluble mediators immune effector cells, IFNγ TNFα, synergize in induction cyclooxygenase 2 (COX2), key enzyme prostaglandin (PG)E2 synthesis, subsequent hyperactivation myeloid-derived suppressor cells (MDSC) within tumor microenvironment (TME) ovarian cancer patients. MDSC by resultant overexpression indoleamine 2,3-dioxygenase...