Immune Regulation News 8.44 December 2, 2016 | |
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TOP STORYStudy Reveals New Role for Hippo Pathway in Suppressing Cancer Immunity Previous studies identified the Hippo pathway kinases LATS1/2 as a tumor suppressor, but new research reveals a surprising role for these enzymes in subduing cancer immunity. The findings could have a clinical role in improving efficiency of immunotherapy drugs. [Press release from UC San Diego discussing online prepublication in Cell] Press Release | Abstract | Graphical Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)Tumor Interferon Signaling Regulates a Multigenic Resistance Program to Immune Checkpoint Blockade Researchers demonstrated that prolonged interferon signaling orchestrates PDL1-dependent and PDL1-independent resistance to immune checkpoint blockade and to combinations such as radiation plus anti-CTLA4. Persistent type II interferon signaling allows tumors to acquire STAT1-related epigenomic changes and augments expression of interferon-stimulated genes and ligands for multiple T cell inhibitory receptors. [Cell] Abstract | Graphical Abstract Trans-Presentation of IL-6 by Dendritic Cells Is Required for the Priming of Pathogenic TH17 Cells The authors used a novel strategy for the conditional deletion of distinct interleukin 6 (IL-6)-producing cell types to show that dendritic cells positive for the signaling regulator Sirpα were essential for the generation of pathogenic TH17 cells. [Nat Immunol] Abstract Scientists showed that the mTORC1–PPARγ pathway is crucial for the fatty acid uptake programme in activated CD4+ T cells. This pathway is required for full activation and rapid proliferation of naive and memory CD4+ T cells. [Nat Commun] Full Article The authors showed that early growth response gene 2 (Egr2) and Egr3 expressed in T cells cooperatively prevent humoral immune responses by supporting TGF-β3 secretion. T cell-specific Egr2/Egr3 double-deficient mice spontaneously developed an early onset lupus-like disease that was more severe than in T cell-specific Egr2-deficient mice. [Proc Natl Acad Sci USA] Abstract | Full Article Basophils Promote Tumor Rejection via Chemotaxis and Infiltration of CD8+ T Cells To study the mechanisms controlling tumor rejection, investigators assessed different mouse models for regulatory T-cell (Treg) depletion. In Foxp3DTR knock-in mice, about 99% Treg depletion was achieved, resulting in complete rejection of transplanted HCmel12 melanomas in a CD8+ T cell-dependent way. [Cancer Res] Abstract Scientists demonstrated that aged mice with far fewer naïve T cells, respond to the model antigen, hen eggwhite lysozyme, by utilizing the same T cell receptor sequence as their younger counterparts. [J Autoimmun] Full Article | Graphical Abstract Functional Defects in CD4+ CD25high FoxP3+ Regulatory Cells in Ankylosing Spondylitis Researchers investigated regulatory T cell (Treg) function and found that Tregs in peripheral blood from patients with active ankylosing spondylitis had lower FoxP3 mean fluorescence intensity than those from healthy controls and could not fully suppress naïve T cell proliferation. [Sci Rep] Full Article Ex vivo, SM934 treatment inhibited the bovine type II collagen (CII) induced proliferation and inflammatory cytokines secretion of CII -reactive T cells. In vitro, SM934 impeded the polarization of naïve CD4+ T cells into Tfh cells and the expression of its transcript factor Bcl-6. [Sci Rep] Full Article Batf3 Selectively Determines Acquisition of CD8+ Dendritic Cell Phenotype and Function The authors showed that bone marrow chimeric mice with a deletion of Id2 in the CD11c compartment lose the ability to reject a skin graft expressing a non-self protein antigen or mount a delayed hypersensitivity response. [Immunol Cell Biol] Abstract Scientists studied the role of the peripheral follicular helper T equivalent, the CXCR5+ CD4+ T cells, in diffuse large B cell lymphoma (DLBCL). Data showed that compared to CXCR5– CD4+ T cells, CXCR5+ CD4+ T cells were significantly more effective at promoting the proliferation as well as inhibiting the apoptosis of primary autologous DLBCL tumor cells. [Exp Cell Res] Full Article Immune Modulation of CD4+CD25+ Regulatory T Cells by Zoledronic Acid The authors investigated the immune modulation of regulatory T (Treg) cells by zoledronic acid (ZA). Flow cytometry was used to analyze the phenotypic and immunosuppressive characteristics of Treg cells treated with ZA. [BMC Immunol] Full Article Subscribe to our sister publications: Human Immunology News & Immunology of Infectious Disease News. | |
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REVIEWSThe authors review the current understanding of the potential cellular and molecular mechanisms by which p53 participates in immune regulation and discuss how targeting the p53 pathway can be exploited to alter the immunological landscape of tumors for maximizing therapeutic outcome. [Int J Mol Sci] Full Article Visit our reviews page to see a complete list of reviews in the immune regulation research field. | |
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INDUSTRY NEWSThe Parker Institute for Cancer Immunotherapy and the Cancer Research Institute announced a major collaboration focused on neoantigens. The search for these unique cancer markers has become a robust area of research as scientists believe they may hold the key to developing a new generation of personalized, targeted cancer immunotherapies. [Parker Institute for Cancer Immunotherapy] Press Release ASIT biotech announced today the recruitment of the last patient in its Phase IIa trial with hdm-ASIT+™, its product candidate for house dust mite rhinitis. [ASIT biotech] Press Release Merck announced that the U.S. Food and Drug Administration (FDA) has accepted for review the sBLA for KEYTRUDA®, the company’s anti-PD-1 therapy, for the treatment of patients with refractory classical Hodgkin lymphoma or for patients who have relapsed after three or more prior lines of therapy. [Merck & Co., Inc.] Press Release OncoQuest Announces Positive Interim Results from its Phase IIb Clinical Study OncoQuest Inc. announced positive interim results from the Phase IIb clinical study of its lead product, oregovomab, in patients with advanced epithelial ovarian, adnexal or peritoneal carcinoma. [OncoQuest Inc.] Press Release Agenus Inc. announced that the first patient has been dosed in a Phase I/II clinical trial of the anti-OX40 agonist antibody INCAGN1949. [Agenus Inc.] Press Release | |
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POLICY NEWSUS Health-Reform Legislation Clears Big Hurdle Legislation that would streamline research and development at the US National Institutes of Health and drug regulation at the Food and Drug Administration is one step closer to becoming law. The US House of Representatives approved the nearly 1,000-page bill — known as the 21st Century Cures Act — on 30 November. The Senate is expected to take up the controversial US$6.3-billion measure as early as next week. [Nature News] Editorial Battle over US Overtime Pay Rules Leaves Many Postdocs in Limbo Institutions struggle to respond after court blocks regulations that would have increased wages for junior researchers. Some universities are proceeding with planned salary increases for postdocs, but others have cancelled — or at least, temporarily halted — changes to researchers’ pay. The uncertainty over how the legal battle will play out is already affecting some postdocs’ career and family plans. [Nature News] Editorial FDA Chief Pushes Back against Criticism of Stem Cell Treatment Regulations The country’s top drug regulators pushed back on claims they move too slowly in approving new stem cell treatments and sought to temper expectations for the field’s potential to benefit patients, emphasizing the hazards and the unknowns that persist with developing such therapies. [STAT News] Editorial Big Biology Projects Warm Up to Preprints The 4D Nucleome, a major research consortium funded by the US National Institutes of Health, is now requiring that all manuscripts related to its US$120-million, five-year programme are posted to an online preprint server ahead of peer review. And a privately funded, US$600-million biomedical research initiative in California is considering whether to demand its investigators do the same. [Nature News] Editorial
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JOB OPPORTUNITIESNEW Postdoctoral Fellow – Precision Immunology (Icahn School of Medicine at Mount Sinai) NEW Postdoctoral Research Fellow – Cell Death and Immunity (Fred Hutchinson Cancer Research Center) NEW Postdoctoral Research Fellow – Immune Regeneration (Fred Hutchinson Cancer Research Center) Research Technologist – Cell Separation (STEMCELL Technologies Inc.) Postdoctoral Position – Immunology of HIV-1 and Cancer (University of Alabama at Birmingham) Postdoctoral Researcher – Immunology/Molecular Biology (Duke University Department of Medicine) Postdoctoral Position – Visceral Pain and Neuro-Immune Interaction (KU Leuven) MRC WIMM Prize PhD Studentships – Various Projects (University of Oxford) Assistant Associate or Full Member – Cancer Immunology (Fred Hutchinson Cancer Research Center) Postdoctoral Fellow – Molecular Immunology (University of California, San Diego) Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.
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