1,721,175 research outputs found
From Oncogene Interference to Neutrophil Immune Modulation
No full textOncogenes can aid tumor progression in a cancer cell-extrinsic way. In this issue of Immunity, Glodde et al. (2017) demonstrate that interference with c-MET tyrosine kinase receptor can relieve neutrophil-dependent immune suppression and unleash the effectiveness of immunotherapy even in the context of c-MET-independent tumors. Oncogenes can aid tumor progression in a cancer cell-extrinsic way. In this issue of Immunity, Glodde et al. (2017) demonstrate that interference with c-MET tyrosine kinase receptor can relieve neutrophil-dependent immune suppression and unleash the effectiveness of immunotherapy even in the context of c-MET-independent tumors. © 2017 Elsevier Inc
Wnt–β-catenin as an epigenetic switcher in colonic Treg cells
Full text linkIn the colonic environment, sustained Wnt–β-catenin activation in regulatory T cells promotes epigenetic rewiring toward proinfammatory RORγt + Treg cells, whose expansion parallels the disease progression from infammatory bowel disease (IBD) to manifest colorectal cancer (CRC)
Arginase, Nitric Oxide Synthase, and Novel Inhibitors of L-Arginine Metabolism in Immune Modulation
No full textResponses of mouse lymphocytes to extracellular adenosine 5'-triphosphate (ATP). Lymphocytes with cytotoxic activity are resistant to the permeabilizing effects of ATP
No full textAbstract
The effects of extracellular ATP on plasma membrane permeability in mouse lymphocytes were studied with plasma membrane depolarization, uptake of ethidium bromide, and release of lactate dehydrogenase as indicators of increased permeability. Extracellular ATP induced sustained depolarization of plasma membrane potential as well as uptake of low m.w. fluorescent markers in mouse lymphocytes derived from thymus and spleen, and in two lymphoma lines YAC-1 and MBL-2. The fully ionized form ATP4- rather than MgATP2- mediated the increased permeability of the plasma membrane. Although prolonged exposure to exogenous ATP ultimately lysed the lymphocytes, two CTL populations (CHM-14 clone and CTLL-2 line) and IL-2-treated spleen lymphocytes with unrestricted killing activity were highly resistant to the permeabilizing action of extracellular ATP at all concentrations tested. In addition, CTL derived from primary immune peritoneal exudate and enriched by in vitro culture for 5 days in the presence of specific stimulator cells were also resistant to this permeabilizing effect. These findings show that exogenous ATP has a lytic effect on mouse lymphocytes but not on CTL, and suggest a role for ATP in cell-mediated cytotoxicity
Responses of mouse lymphocytes to extracellular ATP. II Extracellular ATP causes cell type-dependent lysis and DNA fragmentation
Full text linkExtracellular ATP (ATPo) caused dose-dependent lysis of YAC-1 and P-815 mouse tumor cells. This event, assessed by 51Cr release, was accompanied by sustained depolarization of the plasma membrane potential and Ca2+ influx. Plasma membrane depolarization and Ca2+ influx occurred within a few seconds of ATPo addition to both cell types, whereas 51Cr was released without apparent lag in YAC-1 cells and after 2 h in P-815 cells. Furthermore, a rise in [Ca2+]i was required for ATPo-dependent lysis of YAC-1 but not P-815 cells. In P-815 cells, ATPo caused an early and [Ca2+]i-independent DNA fragmentation that occurred at lower nucleotide concentrations than those required to trigger 51Cr release. Instead in YAC-1 cells very low concentrations of ATPo caused early lysis (ED50 for lysis about 200 microM) accompanied by only barely detectable DNA fragmentation. Previous studies disclosed that lymphokine-activated killer cells are fully resistant to the membrane-perturbing effects of ATPo. We show that lymphokine-activated killer cells also do not undergo DNA fragmentation even in the presence of high ATPo concentrations. This study complements previous observations on the lytic effects of ATPo and shows that this nucleotide can also cause DNA fragmentation, one of the earliest target cell alterations observed during CTL-mediated lysis
Altered macrophage differentiation and immune dysfunction in tumor development.
No full textTumors require a constant influx of myelomonocytic cells to support the angiogenesis and stroma remodeling needed for their growth. This is mediated by tumor-derived factors, which cause sustained myelopoiesis and the accumulation and functional differentiation of myelomonocytic cells, most of which are macrophages, at the tumor site. An important side effect of the accumulation and functional differentiation of these cells is that they can induce lymphocyte dysfunction. A complete understanding of the complex interplay between neoplastic and myelomonocytic cells might offer novel targets for therapeutic intervention aimed at depriving tumor cells of important growth support and enhancing the antitumor immune response
Tumor-induced tolerance and immune suppression by myeloid derived suppressor cells
No full textEmerging evidence indicates that the Achilles' heel of cancer immunotherapies is often the complex interplay of tumor-derived factors and deviant host properties, which involve a wide range of immune elements in the lymphoid and myeloid compartments. Regulatory lymphocytes, tumor-conditioned myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages, and dysfunctional and immature dendritic cells take part in a complex immunoregulatory network. Despite the fact that some mechanisms governing tumor-induced immune tolerance and suppression are starting to be better understood and their complexity dissected, little is known about the diachronic picture of immune tolerance. Based on observations of MDSCs, we present a time-structured and topologically consistent idea of tumor-dependent tolerance progression in tumor-bearing hosts
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