Human Immunology News Volume 7.00 | Jan 8 2019

TOP STORY

Gut Immune Cells Cut Inflammation in Multiple Sclerosis

Researchers have discovered that the intestine is the source of immune cells that reduce brain inflammation in people with multiple sclerosis, and that increasing the number of these cells blocks inflammation entirely in a preclinical model of the disease. [Press release from University of California, San Francisco discussing online prepublication in Cell] Press Release | Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

Gene Regulatory Programs Conferring Phenotypic Identities to Human NK Cells

Scientists report integrated “-omics” analysis of human natural killer (NK) subsets, which revealed super-enhancers associated with gene cohorts that may coordinate NK functions and localization. A transcription factor-based regulatory scheme also emerged, which is evolutionarily conserved and shared by innate and adaptive lymphocytes. [Cell] Abstract | Graphical Abstract

RORγt Inhibition Selectively Targets IL-17 Producing iNKT and γδ-T Cells Enriched in Spondyloarthritis Patients

Researchers describe the presence of particular RORγt⁺T-bet^loPLZF⁻ invariant natural killer T (iNKT) and γδ-hi T cell subsets in healthy peripheral blood. RORγt⁺ iNKT and γδ-hi T cells showed IL-23 mediated Th17-like immune responses and were clearly enriched within inflamed joints of spondyloarthritides patients where they act as major IL-17 secretors. [Nat Commun] Full Article

The Signaling Axis Atypical Protein Kinase C λ/ι-Satb2 Mediates Leukemic Transformation of B-Cell Progenitors

Primary human and murine BCR-ABL⁺ leukemic progenitors had increased activation of Cdc42 and the downstream atypical protein kinase C (aPKC). While the isoform aPKCζ behaved as a leukemic suppressor, aPKCλ/ι was critically required for oncogenic progenitor proliferation, survival, and B-cell differentiation arrest, but not for normal B-cell lineage differentiation. [Nat Commun] Full Article

Differential Control of Human Treg and Effector T Cells in Tumor Immunity by Fc-Engineered Anti-CTLA-4 Antibody

Upon in vitro tumor-antigen stimulation of peripheral blood mononuclear cells from healthy individuals or melanoma patients, Fc-region-modified anti-CTLA-4 mAb with high antibody-dependent cell-mediated cytotoxicity and cellular phagocytosis activity selectively depleted CTLA-4⁺FOXP3⁺ Treg cells and consequently expanded tumor-antigen-specific CD8⁺ T cells. [Proc Natl Acad Sci USA] Abstract

Human RIPK1 Deficiency Causes Combined Immunodeficiency and Inflammatory Bowel Diseases

The authors report on eight patients from six unrelated pedigrees with biallelic loss-of-function mutations in receptor-interacting serine/threonine-protein kinase 1 (RIPK1) presenting with primary immunodeficiency and/or intestinal inflammation. [Proc Natl Acad Sci USA] Abstract

Lactate-Mediated Acidification of Tumor Microenvironment Induces Apoptosis of Liver-Resident NK Cells in Colorectal Liver Metastasis

Tissue biopsies were obtained from patients undergoing resection of colorectal liver metastasis, from the tumor, adjacent tissue and distal resection margin. The number and phenotype of liver-resident natural killer cells, at each site, were analyzed by flow cytometry. [Cancer Immunol Res] Abstract

BCL6-Mediated Silencing of PD-1 Ligands in Germinal Center B Cells Maintains Follicular T Cell Population

Acute deletion of Bcl6 in mature germinal center (GC) B cells resulted in marked upregulation of mRNA and protein abundance of programmed cell death protein 1 (PD-1) ligands. Moreover, the expression levels of BCL6 and PD-1 ligands were inversely correlated during GC B cell development and in human GC-derived lymphoma specimens. [J Immunol] Abstract

Ocrelizumab Depletes CD20⁺ T Cells in Multiple Sclerosis Patients

The blood of multiple sclerosis (MS) patients was analyzed with multicolor flow cytometry before and two weeks after treatment with ocrelizumab regarding the phenotype of peripheral blood mononuclear cells. CD20-expressing CD3⁺ T cells were found in blood samples of all MS patients, accounted for 2.4% of CD45⁺ lymphocytes, and constituted a significant proportion of all CD20⁺ cells. [Cells] Full Article

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From Pluripotent Stem Cells to T Cells

The recent development of a 3D artificial organoid model has demonstrated that pluripotent stem cells (PSCs) can generate mature conventional T cells that are fully functional and express a diverse T-cell receptor (TCR) repertoire. Introduction of a transgenic TCR at the PSC stage allows for the production of tumor-antigen-specific, mature conventional T cells. [Exp Hematol] Abstract

Development of Innate Immune Cells from Human Pluripotent Stem Cells

Human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs)-derived natural killer (NK) cells can be produced at a clinical scale suitable for translation into clinical trials. Additionally, pluripotent stem cells can be genetically modified to produce hESC and iPSC-derived human NK cells with enhanced anti-tumor activity. [Exp Hematol] Abstract

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Avalon GloboCare Establishes Joint Venture with Arbele Limited to Co-Develop Next-Generation Multi-Targeted CAR-T Cellular Immunotherapy

Avalon GloboCare Corp. announced that the company and its wholly owned subsidiary, Avactis Biosciences, have entered into a joint venture and exclusive license agreement with Arbele Limited to co-develop next generation, transposon-based Chimeric Antigen Receptor (CAR)-T and CAR-Natural Killer cellular therapies. [Avalon GloboCare Corp.] Press Release

Berkeley Lights Announces Collaboration with University of Pennsylvania to Advance CAR-T Therapeutics

Berkeley Lights, Inc. announced that it has entered into a collaboration to explore multiple lines of inquiry aimed at advancing cellular therapies, including CAR-T therapeutics, with Megan Suhoski Davis, Director of the Product Development Laboratory within the Center for Cellular Immunotherapies in the University of Pennsylvania’s Perelman School of Medicine. [Berkeley Lights, Inc. (PR Newswire Association LLC.)] Press Release

Precigen Announces Clearance of IND to Initiate Phase I/Ib Study for First-in-Class PRGN-3006 UltraCAR-T™ Therapy in Patients with Relapsed or Refractory Acute Myeloid Leukemia (AML) and Higher Risk Myelodysplastic Syndrome (MDS)

Precigen, Inc. announced that the FDA has cleared the Investigational New Drug (IND) application for PRGN-3006, a first-in-class investigational therapy using Precigen’s UltraCAR-T™ platform. [Precigen, Inc. (PR Newswire Association LLC.)] Press Release

Mustang Bio Receives Orphan Drug Designation for MB-102 (CD123 CAR T) for the Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm

Mustang Bio, Inc. announced that the FDA has granted Orphan Drug Designation to MB-102 for the treatment of blastic plasmacytoid dendritic cell neoplasm, a rare and incurable blood cancer with a median survival of less than 18 months and no standard of care. [Mustang Bio, Inc.] Press Release

Donald Trump Finally Has a White House Science Adviser

Nearly two years after he took office, US President Donald Trump has a White House science adviser in place. The Senate confirmed meteorologist Kelvin Droegemeier for the job in a voice vote on 2 January. [Nature News] Editorial

Scientists Despair as US Government Shutdown Drags On

As the shutdown hits the two-week mark with no end in sight, its effects on science have begun to compound, leaving many government researchers weary, worried and demoralized. [Nature News] Editorial

UK Universities Warn ‘No Deal’ Brexit Will Hit Crucial Funding Streams

UK universities have warned the country’s government that leaving the European Union without a deal is “one of the biggest threats” the institutions have ever faced. [Nature News] Editorial

How Much Do Graduate Students Benefit From Studying Abroad?

The National Science Foundation is rethinking how to provide U.S. graduate students with a chance to do science in another country. It also wants to know whether its current foreign travel programs are working. [ScienceInsider] Editorial

Swiss Researchers Struggle to Get Animal Experiments Approved

Scientists say that increasingly rigorous licensing procedures have complicated research efforts—and in some cases, stopped experiments completely. [The Scientist] Editorial

NEW Uncovering Mechanisms of Immune-Based Therapy in Cancer and Autoimmunity
February 18-22, 2019
Breckenridge, Colorado, United States

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NEW Postdoctoral Research Associate – Immunity and Inflammation (University of Illinois – Chicago)

NEW Postdoctoral Fellow – Immunology (Yonsei Cancer Center)

Research Technologist – Immunology (STEMCELL Technologies Inc.)

Research Fellow – Mucosal Immunology (University of Edinburgh)

Postdoctoral Position – Immunology (University of California, San Francisco)

Senior Postdoctoral Scientist/Deputy Group Leader – Immunology (Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases)

Junior Principal Investigator – Immunology (Foundation FIRC Institute of Molecular Oncology)

Assistant/Associate or Professor – Cancer Immunotherapy/Tumor Immunology (University of California, Irvine)

Supervisor – Transfusion Medicine – Immune, Progenitor, & Cell Therapy (Mayo Clinic)

Postdoctoral Position – Natural Killer Cells (The Scripps Research Institute)

Postdoctoral/Staff Scientist – Immune Recognition and Immune Tolerance (Boston Children’s Hospital)

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