Volume 2.47 | Dec 16

Human Immunology News 2.47 December 16, 2014
Human Immunology News
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Licensed Human Natural Killer Cells Aid Dendritic Cell Maturation via TNFSF14/LIGHT
Investigators analyzed the response of human natural killer (NK) cells to tumor cells, and identified a pathway by which NK-dendritic cell interactions occur. Gene expression profiling of tumor-responsive NK cells identified the very rapid induction of TNF superfamily member 14 (TNFSF14/LIGHT), a cytokine implicated in the enhancement of antitumor responses. [Proc Natl Acad Sci USA] Abstract | Full Article
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PUBLICATIONS (Ranked by impact factor of the journal)
Enrichment of ​CD56dimKIR+​CD57+ Highly Cytotoxic NK Cells in Tumor-Infiltrated Lymph Nodes of Melanoma Patients
Investigators show an expansion of ​CD56dim​CD57dim​CD69+​CCR7+KIR+ NK cells in tumor-infiltrated lymph nodes (TILN). TILN NK cells display robust cytotoxic activity against autologous melanoma cells. [Nat Commun] Abstract

IL-28B Is a Key Regulator of B- and T-Cell Vaccine Responses against Influenza
Researchers demonstrate that the presence of the IL-28B TG/GG genotype was associated with increased seroconversion following influenza vaccination. In vitro, recombinant IL-28B increased Th1-cytokines and suppressed Th2-cytokines, H1N1-stimulated B-cell proliferation, and IgG-production. [PLoS Pathog]
Full Article | Editorial

Alarmins MRP8 and MRP14 Induce Stress Tolerance in Phagocytes under Sterile Inflammatory Conditions
During sterile inflammation, polytrauma and burn trauma patients initially present with high serum concentrations of myeloid-related proteins (MRPs). Human neonatal phagocytes are primed for hyporesponsiveness by increased peripartal MRP concentrations, which was confirmed in murine neonatal endotoxinemia in wild-type and MRP14−/− mice. [Cell Rep] Full Article | Graphical Abstract

Phase I/II Study Exploring ImMucin, a Pan-Major Histocompatibility Complex, Anti-MUC1 Signal Peptide Vaccine, in Multiple Myeloma Patients
ImMucin, a 21-mer cancer vaccine encoding the signal peptide domain of the MUC1 tumor-associated antigen, possesses a high density of T- and B-cell epitopes but preserves MUC1 specificity. This Phase I/II study assessed the safety, immunity and clinical response to intradermal ImMucin vaccines. [Br J Haematol] Abstract | Press Release

Foxp3-Mediated Inhibition of Akt Inhibits Glut1 (Glucose Transporter 1) Expression in Human T Regulatory Cells
Freshly isolated human Tregs were unable to up-regulate Glut1 in response to TCR and costimulatory signals compared with Tconv. Consequently, the ability of Tregs to use glucose was also reduced. Introduction of Foxp3 into Tconv inhibited Akt activation and Glut1 expression, indicating that Foxp3 can regulate Glut1. [J Leukoc Biol] Abstract

Melanoma Expression of Matrix Metalloproteinase-23 Is Associated with Blunted Tumor Immunity and Poor Responses to Immunotherapy
Investigators examined the association of matrix metalloproteinase-23 (MMP-23) with the anti-tumor immune response as assessed by the prevalence of tumor-infiltrating lymphocytes and Foxp3+ regulatory T cells. They examined the association between MMP-23 expression and response to immunotherapy. [J Transl Med] Abstract | Full Article

Interleukin-10 Receptor-1 Expression in Monocyte-Derived Antigen-Presenting Cell Populations: Dendritic Cells Partially Escape from IL-10’s Inhibitory Mechanisms
Compared with lymphocytes and various tissue cells and tissues, blood monocytes expressed the highest interleukin-10 receptor-1 (IL-10R1) levels. The in vitro differentiation of these cells into macrophages provoked a further increase of IL-10R1 surface expression. In contrast, their differentiation into myeloid dendritic cells resulted in reduced surface IL-10R1 levels. [Genes Immun] Abstract

Regression of Established Renal Cell Carcinoma in Nude Mice Using Lentivirus-Transduced Human T Cells Expressing a Human Anti-CAIX Chimeric Antigen Receptor
Scientists report on the construction of two chimeric antigen receptors that utilize a carbonic anhydrasedomain mapped, human single chain antibody as a targeting moiety but differ in their capacity to provide costimulatory signaling for optimal T cell proliferation and tumor cell killing. [Mol Ther Oncolytics] Full Article

CD25 Identifies a Subset of CD4+FoxP3TIL that Are Exhausted yet Prognostically Favorable in Human Ovarian Cancer
Researchers hypothesized that CD25, in addition to demarcating regulatory T cells, might identify effector T cells in cancer. To investigate this, they used multi-parameter flow cytometry and immunohistochemistry to analyze tumor-infiltrating lymphocytes (TIL) in primary high-grade serous carcinomas. [Cancer Immunol Res] Abstract

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Regulation of T Cells by mTOR: The Known Knowns and the Known Unknowns
The authors review current understanding of the roles of mammalian/mechanistic target of rapamycin (mTOR) in T cell biology, highlighting emerging concepts and areas of investigation where the precise role of mTOR has yet to be fully discerned. [Trends Immunol] Abstract

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MacroGenics Announces Presentation of Pre-Clinical Data on New DART® Candidate MGD011
MacroGenics, Inc. announced the presentation of pre-clinical data for MGD011, a humanized CD19 x CD3 Dual-Affinity Re-Targeting (DART®) protein. [Press release from MacroGenics Inc. discussing research presented at the 56th Annual Meeting of the American Society of Hematology (ASH), San Francisco] Press Release

Immunotherapy Shows Clinical Benefit in Relapsed Transplant Recipients
A multicenter Phase I trial of the immune checkpoint blocker ipilimumab found clinical benefit in nearly half of blood cancer patients who had relapsed following allogeneic stem cell transplantation. [Press release from Dana-Farber Cancer Institute discussing research presented at the 56th Annual Meeting of the American Society of Hematology (ASH), San Francisco] Press Release

Seattle Children’s Reprogrammed T Cell Immunotherapy Clinical Trial Boasts 85% Complete Remission Rate in Children with Relapsed Leukemia
Seattle Children’s announced that 11 of the 13 patients treated thus far in a clinical trial using genetically reprogrammed T cells to treat relapsed acute lymphoblastic leukemia have achieved complete remission. [Press release from Seattle Children’s Hospital discussing research presented at the 56th Annual Meeting of the American Society of Hematology (ASH), San Francisco] Press Release

Amgen and AstraZeneca Present Results from Phase III AMAGINE-1™ Study Evaluating Brodalumab in Patients with Moderate-to-Severe Plaque Psoriasis
Amgen and AstraZeneca announced that additional results from AMAGINE-1™, a pivotal, multi-arm Phase III trial evaluating two doses of brodalumab in patients with moderate-to-severe plaque psoriasis was presented. [Press release from Amgen Inc. discussing research presented at Psoriasis: From Gene to Clinic International Congress, London ] Press Release

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BC Cancer Agency Researchers Co-Lead $60 Million National Initiative for Innovative Cancer Treatments
BC Cancer Agency researchers will play a key role in the first Network of Centers of Excellence devoted to cancer research, announced today with a $25 million commitment from the Government of Canada and an additional $35 million from partners across the country. [BC Cancer Agency] Press Release

iTeos Therapeutics Announces License and Collaboration with Pfizer Inc. for Discovery and Development of Cancer Immunosuppression Targets
iTeos Therapeutics SA announced a strategic collaboration with Pfizer Inc. pursuant to which iTeos will license to Pfizer rights to iTeos’ pre-clinical compounds targeting Indoleamine 2,3-dioxygenase and Tryptophan 2,3-dioxygenase. [iTeos Therapeutics SA] Press Release

Head-to-Head Psoriasis Study Demonstrates Superiority of Novartis Cosentyx™ to Stelara® in Clearing Skin
Novartis announced that the Phase IIIb CLEAR study for Cosentyx™ (secukinumab) demonstrated superiority to Stelara® (ustekinumab) and met its primary endpoint of achieving clear or almost clear skin at week 16 for psoriasis patients. [Novartis AG] Press Release
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NEW Keystone Symposium – Antibodies as Drugs: Immunological Scaffolds as Therapeutics
February 8-March 13, 2015
Banff, Canada

NEW 9th World Immune Regulation Meeting
March 18-21, 2015
Davos, Switzerland

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NEW Postdoctoral Fellow – Tyrosine Phosphatase in Rheumatoid Arthritis (La Jolla Institute for Allergy & Immunology)

Postdoctoral Research Associate – Immunology (University of Edinburgh)

Investigator – Gut Mucosal Immunology Research (Novartis Institutes for BioMedical Research)

Senior Research Fellow – Immune Response in Aging/Persistent Infections (Singapore Immunology Network A*STAR)

Faculty Position – Department of Microbiology and Immunology (Indiana University School of Medicine)

Postdoctoral Position – Mucosal Immunology (Karolinska Institute)

Postdoctoral Fellow – Immunology (Hospital for Special Surgery)

Postdoctoral Fellow – Translational Medicine and Tumor Immunology (Medical University of Warsaw)

Product Manager Global Marketing – Autoimmunity (Thermo Fisher Scientific)

Scientist – Recombinant Molecules and Antibodies (STEMCELL Technologies Inc.)

Scientist – Pluripotent Stem Cell Media Development, High Throughput Screening (STEMCELL Technologies Inc.)

Scientist – Cell Culture Support Products (STEMCELL Technologies Inc.)

Scientist – Immunology/Cell Separation (STEMCELL Technologies Inc.)

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