Volume 8.00 | Jan 8

Immune Regulation News 8.00 January 8, 2016
Immune Regulation News
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The Neutrophil Btk Signalosome Regulates Integrin Activation during Sterile Inflammation
Scientists examined the molecular mechanisms of leukocyte recruitment to sites of focal hepatic necrosis in vivo. They demonstrated that the Bruton’s tyrosine kinase (Btk) was required for multiple Mac-1 activation events involved in neutrophil recruitment and functions during sterile inflammation triggered by fMLF. [Immunity] Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)
Regulation of T Cell Receptor Signaling by DENND1B in TH2 Cells and Allergic Disease
To understand how DENND1B may contribute to human disease, Dennd1b−/− mice were generated and exhibited hyper-allergic responses following antigen challenge. Dennd1b−/− TH2, but not other TH cells, exhibited delayed receptor-induced T cell receptor (TCR) downmodulation, enhanced TCR signaling, and increased production of effector cytokines. [Cell] Abstract | Graphical Abstract

Interleukin-23-Induced Transcription Factor Blimp-1 Promotes Pathogenicity of T Helper 17 Cells
Researchers identified the transcription factor Blimp-1 as a key interleukin-23-induced factor that drove the inflammatory function of T helper 17 (Th17) cells. In contrast to thymic deletion of Blimp-1, which causes T cell development defects and spontaneous autoimmunity, peripheral deletion of this transcription factor resulted in reduced Th17 activation and reduced severity of autoimmune encephalomyelitis. [Immunity] Abstract

Interleukin-2-Dependent Allergen-Specific Tissue-Resident Memory Cells Drive Asthma
Scientists generated reagents to understand how endogenous CD4+ T cells specific for a house dust mite allergen form and function. Experimental blockade of lymphocyte migration demonstrated that lung-resident cells were sufficient to induce airway hyper-responsiveness, which depended upon CD4+ T cells. [Immunity] Abstract

The Transcription Factor BACH2 Promotes Tumor Immunosuppression
Investigators demonstrated that BACH2 is required to establish immunosuppression within tumors. Tumor growth was markedly impaired in Bach2-deficient mice and coincided with intratumoral activation of both innate and adaptive immunity. [J Clin Invest] Full Article

Stepwise B-Cell-Dependent Expansion of T Helper Clonotypes Diversifies the T-Cell Response
The authors report that clonal selection of CD4+ T cells is extrinsically regulated by B cells. Clonal expansion of lower-avidity T-cell clonotypes depends on availability of MHC II-expressing B cells, in turn influenced by B-cell activation. [Nat Commun] Full Article

IL-7 Signaling Represses Bcl-6 and the TFH Gene Program
Scientists demonstrated that in response to decreased IL-2 signaling, T helper 1 cells upregulate Bcl-6 and co-initiate CD4+ T follicular helper (TFH) – and central memory T-like gene programs, including expression of the cytokine receptors IL-6Rα and IL-7R. [Nat Commun] Full Article | Press Release

T Cell Help Amplifies Innate Signals in CD8+ DCs for Optimal CD8+ T Cell Priming
Investigators showed that CD8+ T cell priming upon HSV-1 skin infection depended on DCs receiving stimulation from both IFN-α/β and CD4+ T cells to provide IL-15. They also observed that increased innate stimulation reversed the helper dependence of CD8+ T cell priming and that the innate stimulus, rather than the CD4+ T cells themselves, determined how “help” was integrated into the priming response by DCs. [Cell Rep] Full Article | Graphical Abstract

Mast Cells Contribute to Autoimmune Diabetes by Releasing Interleukin-6 and Failing to Acquire a Tolerogenic IL-10+ Phenotype
Researchers demonstrated that mast cells (MCs) play a crucial role in type 1 diabetes pathogenesis so that their selective depletion in conditional MC knockout non-obese diabetic mice protects them from the disease. [Clin Immunol] Abstract

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Self-Regulation and Cross-Regulation of Pattern-Recognition Receptor Signaling in Health and Disease
A complex interplay between pattern-recognition receptors and/or other immune pathways finely tunes the outcome of host immune defense responses. The author describes many of the numerous distinct mechanisms for the self-regulation and cross-regulation of innate immune receptor signaling. [Nat Rev Immunol] Abstract

Humanized Hemato-Lymphoid System Mice
The authors review the achievements, most recent developments, and the remaining challenges in the generation of pre-clinically-predictive systems for human hematology and immunology, closely resembling the human situation in a xenogeneic mouse environment. [Haematologica] Full Article

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Roche Presents Updated Results for Investigational Cancer Immunotherapy Atezolizumab in Advanced Bladder Cancer
Roche announced updated results from the pivotal Phase II study, IMvigor 210, of the investigational cancer immunotherapy atezolizumab in people with locally advanced or metastatic urothelial carcinoma. [Press release from F. Hoffmann-La Roche Ltd. discussing research presented at the 2016 Genitourinary Cancers Symposium, San Francisco] Press Release

Celsion Reports Translational Research Data from Its Phase Ib Study of GEN-1 Immunotherapy in Recurrent Ovarian Cancer
The new data demonstrate that intraperitoneally-administered GEN-1 produces an immunologically distinct IL-12 protein that is localized at the tumor site and lasts for up to one week after a single treatment. [Celsion Corporation] Press Release

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Pfizer Enters into Translational Research Collaboration with Adaptive Biotechnologies to Help Advance Novel Immuno-Oncology Solutions
Under the terms of the agreement, Pfizer and Adaptive will seek to combine drug development and platform technology biomarker expertise to identify patients who may preferentially benefit from immunotherapy. [Pfizer Inc.] Press Release

MD Anderson and Kymab Announce Research and Development Strategic Partnership in Immuno-Oncology
Kymab and The University of Texas MD Anderson Oncology Research for Biologics and Immunotherapy Translation unit announced a strategic cancer drug discovery and development alliance. The alliance seeks to discover and develop novel human therapeutic antibodies to treat a variety of cancers. [The University of Texas MD Anderson Cancer Center] Press Release

OncoResponse and Oregon Health & Science University Collaborate to Identify Novel Immuno-Oncology Targets
OncoResponse and the Knight Cancer Institute at Oregon Health & Science University announced a collaboration to identify antibodies against novel targets in elite responders to cancer immunotherapy. [OncoResponse Inc.] Press Release

NCCN Awarded $2 Million in Research Funding from Peregrine Pharmaceuticals to Study Bavituximab in Various Cancers
The National Comprehensive Cancer Network® (NCCN®) Oncology Research Program has been awarded a $2-million grant from Peregrine Pharmaceuticals, Inc. to study bavituximab, a first-in-class treatment approach for various cancers. [National Comprehensive Cancer Network®] Press Release

Transgene Announces First Patient Randomized in Multinational Phase III Trial for Pexa-Vec Oncolytic Immunotherapy in Advanced Liver Cancer
Transgene S.A. announced the initiation of a multinational, randomized Phase III open label study with the oncolytic immunotherapy, Pexa-Vec, in patients with advanced liver cancer, also known as hepatocellular carcinoma. [Transgene S.A.] Press Release
National Institutes of Health (United States)

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)
NEW Cell Culture World Congress USA 2016
May 19-20, 2016
San Diego, United States

NEW 16th International Congress of Immunology
August 21-26, 2016
Melbourne, Australia

Visit our events page to see a complete list of events in the Immune Regulation community.
NEW Postdoctoral Fellow – Cell Therapy (Toronto Western Hospital)

NEW Postdoctoral Position – Immunology (Indiana University)

NEW Postdoctoral Fellow – Immunology (Victoria University of Wellington)

Senior Scientist – Immunology and Cell Separation (STEMCELL Technologies Inc.)

Postdoctoral Position – Immunology (VIB)

PhD Position – Immunology (VIB)

Postdoctoral Research Fellow – Immunity (Massachusetts General Hospital & Harvard Medical School)

Postdoctoral Position – Immunotherapy Targeting Cancer Stem Cells (Ecole Polytechnique Fédérale de Lausanne)

Postdoctoral Position – Cancer Immunotherapy (Bayer HealthCare AG)

Researchers – Immunotherapy (ISPIC Consortium Members)

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