63 research outputs found

    Comparative genomics reveals 104 candidate structured RNAs from bacteria, archaea, and their metagenomes

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    Novel motifs identified in a comparative genomic analysis of bacterial, archaeal and metagenomic data reveals over 100 candidate structured RNAs

    Virus Recognition by Toll-7 Activates Antiviral Autophagy in Drosophila

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    SummaryInnate immunity is highly conserved and relies on pattern recognition receptors (PRRs) such as Toll-like receptors (identified through their homology to Drosophila Toll) for pathogen recognition. Although Drosophila Toll is vital for immune recognition and defense, roles for the other eight Drosophila Tolls in immunity have remained elusive. Here we have shown that Toll-7 is a PRR both in vitro and in adult flies; loss of Toll-7 led to increased vesicular stomatitis virus (VSV) replication and mortality. Toll-7, along with additional uncharacterized Drosophila Tolls, was transcriptionally induced by VSV infection. Furthermore, Toll-7 interacted with VSV at the plasma membrane and induced antiviral autophagy independently of the canonical Toll signaling pathway. These data uncover an evolutionarily conserved role for a second Drosophila Toll receptor that links viral recognition to autophagy and defense and suggest that other Drosophila Tolls may restrict specific as yet untested pathogens, perhaps via noncanonical signaling pathways

    Immune Checkpoint Inhibition in Hodgkin Lymphoma

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    Abstract. Intricate systems of checkpoints such as the programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) axis regulate adaptive immune responses to protect against tissue damage. However, diverse cancers can exploit these pathways to evade or suppress antitumor immunity, leading to tumor progression. Correspondingly, immune checkpoint inhibitors that block PD-1/PD-L1 signaling have shown marked therapeutic efficacy in certain cancers, such as Hodgkin lymphoma. Reed-Sternberg cells, the hallmark cells of Hodgkin lymphoma, commonly overexpress PD-1 ligands, and recent clinical trials have demonstrated impressive response rates with the PD-1 inhibitors nivolumab and pembrolizumab in relapsed or refractory Hodgkin lymphoma, leading to their FDA approval in this setting. Current efforts are underway to improve clinical responses by incorporating PD-1 inhibitors into earlier treatment regimens and identifying therapeutic agents that synergize with PD-1 inhibitors. This review summarizes our understanding of the PD-1/PD-L1 axis in Hodgkin lymphoma, recent clinical studies of anti-PD-1 monotherapy and promising combination immunotherapy in the pipeline

    Gastric Cancer and the Immune System: The Key to Improving Outcomes?

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    Gastric adenocarcinoma is by far the most common form of gastric cancer (GC) and is a highly lethal form of cancer arising from the gastric epithelium. GC is an important area of focus of the medical community, given its often late-stage of diagnosis and associated high mortality rate. While surgery and chemotherapy remain the primary treatments, attention has been drawn to the use of immunologic therapies, which have shown promise in the treatment of other malignancies. The role for immune-based therapies has become clearer as we obtain a greater understanding of the role of the immune system in gastric cancer formation and growth. A variety treatment to augment the immune system are under evaluation in clinical trials, and these include immune checkpoint inhibitors, antibody-drug conjugates, and immune cell-based therapies. Here, we review the immune landscape and immune-based therapies for GC
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