Immune Regulation News Volume 10.24 | Jun 29 2018

TOP STORY

Immunotherapy Drug for Skin Disease Could Boost Hormone Treatment for Prostate Cancer

A new form of immunotherapy reactivates the response to hormone treatment in advanced prostate cancer, a study in mice and human prostate cancer cells has found. Hormone therapy is a mainstay of prostate cancer treatment – but tumor cells can grow resistant, leading to a hard-to-treat, advanced form of the disease. Scientists found that blocking a protein produced by a type of immune cell – known as granulocytic myeloid-derived suppressor cells – restored sensitivity to hormone therapy. [Press release from The Institute of Cancer Research discussing online prepublication in Nature] Press Release | Abstract

(Ranked by impact factor of the journal)

Induction of Innate Immune Memory via MicroRNA Targeting of Chromatin Remodeling Factors

Investigators performed a screen for tolerance-associated microRNAs and identified miR-221 and miR-222 as regulators of the functional reprogramming of macrophages during lipopolysaccharide tolerization. Prolonged stimulation with lipopolysaccharide in mice led to increased expression of miR-221 and mir-222, both of which regulate brahma-related gene 1. [Nature] Abstract

A Human Anti-IL-2 Antibody that Potentiates Regulatory T Cells by a Structure-Based Mechanism

Researchers report the generation of a fully human anti-interleukin-2 (IL-2) antibody, F5111.2, that stabilized IL-2 in a conformation that results in the preferential STAT5 phosphorylation of T_regs in vitro and selective expansion of T_regs in vivo. [Nat Med] Abstract

Tumor Cell-Intrinsic Factors Underlie Heterogeneity of Immune Cell Infiltration and Response to Immunotherapy

To understand the factors underlying tumor immune heterogeneity and immunotherapy sensitivity, the authors established a library of congenic tumor cell clones from an autochthonous mouse model of pancreatic adenocarcinoma. These clones generated tumors that recapitulated T cell-inflamed and non-T-cell-inflamed tumor microenvironments upon implantation in immunocompetent mice, with distinct patterns of infiltration by immune cell subsets. [Immunity] Abstract | Graphical Abstract

Iron Drives T Helper Cell Pathogenicity by Promoting RNA-Binding Protein PCBP1-Mediated Proinflammatory Cytokine Production

Researchers showed that iron promoted proinflammatory cytokine expression in T cells, including GM-CSF and IL-2, via regulating the stability of an RNA-binding protein PCBP1. Iron depletion or Pcbp1 deficiency in T cells inhibited GM-CSF production by attenuating Csf2 3′ untranslated region activity and messenger RNA stability. [Immunity] Abstract | Press Release | Graphical Abstract

The E3 Ligases Itch and WWP2 Cooperate to Limit T_H2 Differentiation by Enhancing Signaling through the TCR

CD4⁺ T cells deficient in Itch and WWP2 exhibited hypo-responsiveness to T cell antigen receptor (TCR) stimulation and a bias toward differentiation into the T_H2 subset of helper T cells. [Nat Immunol] Abstract

Epstein-Barr Virus-Encoded EBNA2 Alters Immune Checkpoint PD-L1 Expression by Downregulating miR-34a in B-Cell Lymphomas

Scientists found that latency III-expressing Burkitt lymphoma, diffuse large B-cell lymphomas (DLBCL) or their EBNA2-transfected derivatives express high PD-L1. In a DLBCL model, EBNA2 but not LMP1 is sufficient to induce PD-L1. [Leukemia] Abstract

IKZF1 Enhances Immune Infiltrate Recruitment in Solid Tumors and Susceptibility to Immunotherapy

The authors showed that overexpression of the master regulator IKZF1 leads to enhanced immune infiltrate recruitment and tumor sensitivity to PD1 and CTLA4 inhibitors in several tumors that normally lack IKZF1 expression. [Cell Syst] Abstract | Graphical Abstract

Neutrophils Kill Antibody-Opsonized Cancer Cells by Trogoptosis

Researchers demonstrated that neutrophils can exert a mode of destruction of cancer cells, which involves antibody-mediated trogocytosis by neutrophils. Intimately associated with this is an active mechanical disruption of the cancer cell plasma membrane, leading to a lytic type of cancer cell death. [Cell Rep] Full Article | Graphical Abstract

Mitochondria Maintain Controlled Activation State of Epithelial-Resident T Lymphocytes

Intraepithelial lymphocytes (IELs) are kept in a heightened state of activation resembling effector T cells but without cytokine production or clonal proliferation. Scientists showed that this controlled activation state correlates with alterations in the IEL mitochondrial membrane, especially the cardiolipin composition. [Sci Immunol] Abstract | Press Release

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Promises and Limitations of Immune Cell-Based Therapies in Neurological Disorders

Investigators highlight discoveries on the beneficial functions of regulatory immune cells and their mechanisms of action and evaluate their potential use as novel cell-based therapies for brain disorders. [Nat Rev Neurol] Abstract

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AbbVie and Calibr Announce Collaboration for Next Generation T-Cell Therapies

AbbVie and Calibr announced a collaboration to develop T-cell therapies aimed primarily at cancer, including solid tumors. [AbbVie Inc.] Press Release

BioAtla Announces First Patient Treated in Phase I/II BA3021-001 Clinical Trial for CAB-ROR2-ADC Therapeutic

BioAtla, LLC announced the treatment of the first patient in its clinical trial BA3021-001 for BioAtla’s BA3021, a novel conditionally active ROR2-targeted antibody-drug conjugate (CAB-ROR2-ADC). [BioAtla, LLC (PR Newswire Association LLC.)] Press Release

Rigel Initiates Phase I Clinical Trial of R835, an IRAK1/4 Inhibitor for Autoimmune and Inflammatory Diseases

Rigel Pharmaceuticals, Inc. announced that it has initiated a Phase I study to assess safety, tolerability, pharmacokinetics and pharmacodynamics of R835 in healthy subjects. Rigel selected R835, a proprietary molecule from its interleukin receptor associated kinase (IRAK) preclinical development program, for human clinical trials. [Rigel Pharmaceuticals, Inc.] Press Release

Ziopharm Oncology Enrolls First Patient in Phase I Trial Evaluating Combination Therapy of Controlled IL-12 and OPDIVO^®

Ziopharm Oncology, Inc. announced that it has enrolled the first patient in its Phase I clinical trial to evaluate Ad-RTS-hIL-12 plus veledimex in combination with OPDIVO^®, an immune checkpoint, or PD-1, inhibitor, in adult patients with recurrent glioblastoma. [Ziopharm Oncology, Inc.] Press Release

Macchiarini Guilty of Misconduct, but Whistleblowers Share Blame, New Karolinska Institute Verdict Finds

The Karolinska Institute in Stockholm has finally, officially, found disgraced surgeon Paolo Macchiarini guilty of scientific misconduct. However, the verdict is a bitter pill for the four people who raised the alarm about Macchiarini’s fraud. [ScienceInsider] Editorial

Top US Court Upholds Trump Travel Ban: Student Visas Already in Decline

The travel restrictions now vary by country, and include some exemptions for students. But data from the Department of Justice reveal that the government issued just 289 visas to students from Iran, Libya, Yemen and Somalia in the first three months of this year. [Nature News] Editorial

NEW 47^th Annual Scientific Meeting of the Australasian Society for Immunology
December 2-6, 2018
Perth, Australia

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NEW Professorship – Molecular Immune Regulation (Kiel University)

Research Technologist – Cell Separation (STEMCELL Technologies Inc.)

Postdoctoral Fellowships – Immunometabolism (St. Jude Children’s Research Hospital)

Assistant/Associate Professor – Immunology (University of Massachusetts)

PhD Student – Cellular Immunotherapy (Glycostem Therapeutics)

Postdoctoral Research Fellow – Human Systems Immunology (University of Oslo)

PhD Position – Characterization of the Immune Pathways that Stimulate Autoimmunity Caused By ADAR1 Deficiency (VIB)

PhD Student Positions – Immunology (Multiple Locations)

Postdoctoral Research Scientist – Immunology (Lilly)

Postdoctoral Fellowship – Immunology (University of South Carolina)

Postdoctoral Position – Tumor Immunology and Cancer Immunotherapy (Vlaams Instituut voor Biotechnologie)

Postdoctoral Fellow – Immunology (Boston University School of Medicine)

Postdoctoral Fellow – Innate Immune Signaling (Houston Methodist Research Institute)

Postdoctoral Associate Position – Tumor Immunology/Immunotherapy (Duke Cancer Institute)

Assistant, Associate, or Full Member – Cancer Immunology (Fred Hutchinson Cancer Research Center)

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