A5057788524- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- Chemokine receptors and signaling
- T-cell and B-cell Immunology
- CAR-T cell therapy research
- Immune cells in cancer
- interferon and immune responses
- Immune Response and Inflammation
- Monoclonal and Polyclonal Antibodies Research
- RNA Interference and Gene Delivery
- Colorectal Cancer Treatments and Studies
- vaccines and immunoinformatics approaches
- Inflammatory mediators and NSAID effects
- Ovarian cancer diagnosis and treatment
- Cancer, Stress, Anesthesia, and Immune Response
- Virus-based gene therapy research
- Cytokine Signaling Pathways and Interactions
- Cancer Research and Treatments
- Brain Metastases and Treatment
- RNA regulation and disease
- Receptor Mechanisms and Signaling
- Ferroptosis and cancer prognosis
- Glioma Diagnosis and Treatment
- Colorectal Cancer Surgical Treatments
UPMC Hillman Cancer Center
2014-2025
Roswell Park Comprehensive Cancer Center
2011-2025
University of Pittsburgh
2012-2024
Moffitt Cancer Center
2024
Bipar
2021
University at Buffalo, State University of New York
2019
Pittsburg State University
2015
Bioengineering Center
2015
Data Harbor (United States)
2015
Magee-Womens Research Institute
2011-2013
We studied to what extent the presence of an inflammatory mediator PGE2, during development dendritic cells (DC) affects their subsequent ability induce Th1- and Th2-type cytokines in maturing naive Th cells. PGE2 (10(-9)-10(-6) M) did not alter morphology or expression class II MHC costimulatory molecules on DC obtained from monocytes granulocyte-macrophage CSF IL-4, although at concentrations above 10(-8) M, prevented acquisition CD1a marker. Both control (PGE2-DC) were potent stimulators...
A phase I/II trial was performed to evaluate the safety and immunogenicity of a novel vaccination with α-type 1 polarized dendritic cells (αDC1) loaded synthetic peptides for glioma-associated antigen (GAA) epitopes administration polyinosinic-polycytidylic acid [poly(I:C)] stabilized by lysine carboxymethylcellulose (poly-ICLC) in HLA-A2(+) patients recurrent malignant gliomas. GAAs these are EphA2, interleukin (IL)-13 receptor-α2, YKL-40, gp100.Twenty-two (13 glioblastoma multiforme [GBM],...
Abstract Dendritic cells (DC) are key initiators of primary immune responses. Myeloid DC can secrete IL-12, a potent Th1-driving factor, and often viewed as Th1-promoting APC. Here we show that neither Th1- nor Th2-inducing function is an intrinsic attribute human myeloid DC, but both depend on environmental instruction. Uncommitted immature require exposure to IFN-γ, at the moment induction their maturation or shortly thereafter, develop capacity produce high levels IL-12p70 upon subsequent...
Abstract Upon microbial infection, specific Th1 or Th2 responses develop depending on the type of microbe. Here, we demonstrate that different compounds polarize maturation human myeloid dendritic cells (DCs) into stably committed cell-promoting (DC1) (DC2) effector DCs Th via mechanisms. Protein extract derived from helminth Schistosoma mansoni induced development DC2s promote enhanced expression OX40 ligand. Likewise, toxin extracellular bacterium Vibrio cholerae as well, however, an...
Abstract PGE2 is a well known immunomodulator that has multiple effects on the immune system. We demonstrate selectively and dose dependently inhibits IL-2 IFN-gamma production by mitogenically stimulated human PBL CD4+ TLC, although at low concentrations IL-4 not affected IL-5 even up-regulated. In tested induced dramatic elevation (up to 85-fold) of intracellular cAMP levels. The action may, therefore, be associated with levels, affecting differentially from production. To test this...
Abstract Using the principle of functional polarization dendritic cells (DCs), we have developed a novel protocol to generate human DCs combining three features critical for induction type-1 immunity: (a) fully mature status; (b) responsiveness secondary lymphoid organ chemokines; and (c) high interleukin-12p70 (IL-12p70)-producing ability. We show that IFN-α polyinosinic:polycytidylic acid (p-I:C) synergize with “classical” type-1-polarizing cytokine cocktail [tumor necrosis factor α...
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...
Abstract Both anti-PD1/PD-L1 therapy and oncolytic virotherapy have demonstrated promise, yet exhibited efficacy in only a small fraction of cancer patients. Here we hypothesized that an poxvirus would attract T cells into the tumour, induce PD-L1 expression immune cells, leading to more susceptible targets for anti-PD-L1 immunotherapy. Our results demonstrate colon ovarian models vaccinia virus attracts effector induces on both tumour. The dual reduces + facilitates non-redundant tumour...
Abstract Activation of immature dendritic cells (DC) in peripheral tissues induces their migration to lymph nodes and maturation into CD83+ DC, which are able prime naive T cells. The inflammatory cytokines IL-1β TNF-α induce mature can secrete IL-12 promote the development Th0/Th1-biased DC factors with a Th2-promoting function have not been described. Here we show that PGE2, although it does final by itself, synergizes TNF-α, allows effectiveness at 100-fold lower concentrations. While...
Early stages of viral infections are associated with local recruitment and activation dendritic cells (DC) NK cells. Although activated DC known to support each other's functions, it is less clear whether their interaction in infected tissues can modulate the subsequent ability migrating induce T cell responses draining lymph nodes. In this study, we report that capable inducing stable type 1-polarized "effector/memory" (DC1) act as carriers cell-derived helper signals for development 1...
In addition to their cytotoxic activities, natural killer (NK) cells can have immunoregulatory functions. We describe a distinct “helper” differentiation pathway of human CD56+CD3− NK into CD56+/CD83+/CCR7+/CD25+ that display high migratory responsiveness lymph node (LN)–associated chemokines, ability produce interferon-γ upon exposure dendritic cell (DC)- or T helper (Th) cell–related signals, and pronounced abilities promote interleukin (IL)-12p70 production in DCs the development Th1...
Abstract Activation of immature CD83− dendritic cells (DC) in peripheral tissues induces their maturation and migration to lymph nodes. Activated DC become potent stimulators Th efficient inducers Th1- Th2-type cytokine production. This study analyzes the ability human monocyte-derived CD1a+ at different stages IL-1β TNF-α-induced produce major Th1-driving factor IL-12. early (2 4 h) produced elevated amounts IL-12 p70 during interaction with CD40 ligand-bearing or, after stimulation T...
Abstract Preferential activation of regulatory T (Treg) cells limits autoimmune tissue damage during chronic immune responses but can also facilitate tumor growth. Here, we show that tissue-produced inflammatory mediators prime maturing dendritic (DC) for the differential ability attracting anti-inflammatory Treg cells. Our data prostaglandin E2 (PGE2), a factor overproduced in inflammation and cancer, induces stable Treg-attracting properties DC, mediated by CCL22. The elevated production...
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...