Human Immunology News Volume 5.49 | Dec 12 2017

TOP STORY

High-Dimensional Phenotypic Mapping of Human Dendritic Cells Reveals Interindividual Variation and Tissue Specialization

Scientists performed a multiparametric phenotypic characterization and unbiased analysis of human dendritic cell (DC) subsets in blood, tonsil, spleen, and skin. They uncovered previously unreported phenotypic heterogeneity of human cDC2s among individuals, including variable expression of functional receptors such as CD172a. [Immunity] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

Matrix Metalloproteinase-9 Might Affect Adaptive Immunity in Non-ST Segment Elevation Acute Coronary Syndromes by Increasing CD31 Cleavage on CD4⁺ T-Cells

The authors investigated the mechanisms underlying CD31 dysregulation in acute coronary syndrome (ACS). Their study suggests that enhanced matrix metalloproteinase-9 release plays a key role in determining the cleavage and shedding of the functional CD31 domain 1–5 in CD4⁺ T-cells of ACS patients. [Eur Heart J] Full Article

PGE₂ Suppresses Human Group 2 Innate Lymphoid Cell Function

Scientists investigated how PGE₂ regulates human group 2 innate lymphoid cells (ILC2) function. PGE₂ inhibited the expression of GATA3, as well as the production of type 2 cytokines, IL-5 and IL-13, from human tonsil and blood ILC2 in response to stimulation with a combination of IL-25, IL-33, TSLP and IL-2. [J Allergy Clin Immunol] Abstract | Full Article | Graphical Abstract

Human CD26^high T Cells Elicit Tumor Immunity against Multiple Malignancies via Enhanced Migration and Persistence

The authors exhibited that CD26 identifies three T helper subsets with distinct immunological properties in both healthy individuals and cancer patients. Although CD26^neg T cells possessed a regulatory phenotype, CD26^int T cells were mainly naive and CD26^high T cells appeared terminally differentiated and exhausted. [Nat Commun] Full Article

Multidimensional Analysis Integrating Human T-Cell Signatures in Lymphatic Tissues with Sex of Humanized Mice for Prediction of Responses after Dendritic Cell Immunization

Analyses of human T cell maturation in humanized models have been hampered by an overall low immune reactivity and lack of methods to define predictive markers of responsiveness. Researchers evaluated the effects of mouse sex in the dynamics of T cell homing and maturation status in thymus, blood, bone marrow, spleen, and lymph nodes. [Front Immunol] Full Article

Dominant Role of Microglial and Macrophage Innate Immune Responses in Human Ischemic Infarcts

Scientists performed a quantitative study on the inflammatory reaction in human ischemic infarct lesions. They found increased numbers of T-lymphocytes, mainly CD8⁺ cells, but not of B-lymphocytes. [Brain Pathol] Abstract

Human Leukocyte Antigen-G Inhibits the Anti-Tumor Effect of Natural Killer Cells via Immunoglobulin-Like Transcript 2 in Gastric Cancer

The authors investigated the expression of human leukocyte antigen-G (HLA-G) in gastric cancer (GC) and the role of HLA-G-effected natural killer (NK) cells in GC progression. The expression of HLA-G was negatively associated with the number of tumor-infiltrating NK cells. [Cell Physiol Biochem] Full Article

Long-Term Maintenance of Peripheral Blood Derived Human NK Cells in a Novel Human IL-15-Transgenic NOG Mouse

Scientists generated a novel mouse strain expressing transgenic human IL-15 using the severe immunodeficient NOD/Shi-scid-IL-2Rγ^null (NOG) mouse genetic background (NOG-IL-15 Tg). Human natural killer cells, purified from the peripheral blood of normal healthy donors, proliferated when transferred into NOG-IL-15 Tg mice. [Sci Rep] Full Article

Unbiased Quantitative Proteomics Reveals a Crucial Role of the Allergen Context for the Activation of Human Dendritic Cells

To investigate the allergenicity of the major birch pollen allergen Bet v 1 and the impact of adjuvants associated with pollen, e.g. lipopolysaccharide, researchers performed quantitative proteome analysis to study the activation of monocyte-derived dendritic cells. [Sci Rep] Full Article

CXCL4 Is a Novel Inducer of Human Th17 Cells and Correlates with IL-17 and IL-22 in Psoriatic Arthritis

Investigators demonstrated that CXCL4 induced human CD4 T cells to secrete IL-17 that co-expressed IFNγ and IL-22, and differentiated naïve CD4 T cells to become Th17-cytokine producing cells. In a co-culture system of human CD4 T cells with monocytes or myeloid dendritic cells, CXCL4 induced IL-17 production upon triggering by superantigen. [Eur J Immunol] Abstract

Endoplasmic Reticulum Stress Induced Lox-1⁺CD15⁺ Polymorphonuclear Myeloid-Derived Suppressor Cells in Hepatocellular Carcinoma

Researchers investigated the existence lectin-type oxidized LDL receptor-1 (LOX-1) polymorphonuclears myeloid-derived suppressor cells (PMN-MDSCs) in hepatocellular carcinoma (HCC) patients. LOX-1⁺CD15⁺ PMN-MDSC were significantly elevated in HCC patients compared with healthy control and patients with benign diseases. [Immunology] Abstract

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Towards Personalized, Tumor-Specific, Therapeutic Vaccines for Cancer

Scientists review the emerging field of personalized cancer vaccination and discuss recent developments and future directions for this promising treatment strategy. [Nat Rev Immunol] Abstract

Intestinal Intraepithelial Lymphocytes: Sentinels of the Mucosal Barrier

The authors review sentinel functions of intestinal intraepithelial lymphocytes (IELs) in the maintenance of the mucosal barrier integrity, as well as how dysregulated IEL responses can contribute to pathology. [Trends Immunol] Abstract

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St. Jude Gene Therapy Improves Immunity in Babies with ‘Bubble Boy’ Disease

Early evidence suggests that gene therapy developed at St. Jude Children’s Research Hospital will lead to broad protection for infants with the X-linked severe combined immunodeficiency disorder. [Press release from St. Jude Children’s Research Hospital discussing research presented at the 2017 American Society of Hematology (ASH) Annual Meeting, Atlanta] Press Release

Celgene Corporation and bluebird bio Announce Updated Results from Ongoing Multicenter Phase I Study of bb2121 Anti-BCMA CAR T Cell Therapy in Patients with Late Stage Relapsed/Refractory Multiple Myeloma

Celgene Corporation and bluebird bio, Inc. announced that updated results from the ongoing CRB-401 Phase I clinical study of bb2121, an investigational anti-B-cell maturation antigen (BCMA) CAR T cell therapy, in 21 patients with late-stage relapsed/refractory multiple myeloma were presented in an oral presentation. [Press release from bluebird bio, Inc. discussing research presented at the 2017 American Society of Hematology (ASH) Annual Meeting, Atlanta] Press Release

Magenta Therapeutics’ Expanded Stem Cell Product, MGTA-456, Engrafts in 100% of Patients, Leading to Robust Neutrophil and Immune Recovery in Two Phase II Clinical Studies

Magenta Therapeutics reported Phase II clinical data from its MGTA-456 hematopoietic stem cell (HSC) expansion program. MGTA-456 is a single umbilical cord blood unit expanded with an aryl hydrocarbon receptor antagonist. [Press release from Magenta Therapeutics discussing research presented at the 2017 American Society of Hematology (ASH) Annual Meeting, Atlanta] Press Release

CAR T, Immunotherapy Bring New Hope for Multiple Myeloma Patients

Two investigational immunotherapy approaches, including chimeric antigen receptor (CAR) T cell therapy, have shown encouraging results in the treatment of multiple myeloma patients who had relapsed and were resistant to other therapies. [Press release from the University of Pennsylvania discussing research presented at the 2017 American Society of Hematology (ASH) Annual Meeting, Atlanta] Press Release

City of Hope Physicians Report on New CAR-T Cell Therapy for Acute Myeloid Leukemia, Blastic Plasmacytoid Dendritic Cell Neoplasm

City of Hope patients whose acute myeloid leukemia was no longer responding to standard therapies and a patient with a rare blood cancer, blastic plasmacytoid dendritic cell neoplasm, achieved a complete response after undergoing treatment with MB-102 CAR-T therapy, which targets CD123 cells. [Press release from City of Hope discussing research presented at the 2017 American Society of Hematology (ASH) Annual Meeting, Atlanta] Press Release

Neon Therapeutics Announces Clinical Trial Collaboration with Merck

Neon Therapeutics announced that it has entered a clinical trial collaboration with Merck to evaluate Neon Therapeutics’ proprietary personal neoantigen vaccine, NEO-PV-01, in combination with Merck’s anti-PD-1 therapy, KEYTRUDA^®, along with chemotherapy. [Neon Therapeutics, Inc.] Press Release

Fate Therapeutics and University of California San Diego Launch Research Collaboration to Develop iPSC-Derived CAR NK Cell Cancer Immunotherapies

Fate Therapeutics, Inc. announced a partnership with the University of California, San Diego to develop off-the-shelf, chimeric antigen receptor (CAR)-targeted natural killer (NK) cell cancer immunotherapies. [Fate Therapeutics, Inc.] Press Release

Morphotek and Rockefeller University Form a Sponsored Research Agreement to Study the Immunosuppressive Effects of the Tumor Shed Antigen CA125 and Its Potential Impact in Future Patient Therapies

Morphotek^®, Inc. announced that it has entered into a Sponsored Research Agreement with the Rockefeller University to expand its research efforts around the mechanisms by which the CA125 tumor shed antigen suppresses immune-based therapies. [Morphotek^®, Inc.] Press Release

Palleon Pharmaceuticals Signs Exclusive License Agreement with King’s College London for Intellectual Property Related to Glycoimmune Checkpoints to Treat Cancer

Palleon Pharmaceuticals announced an agreement with King’s College London to license intellectual property developed in the laboratory of Joy Burchell, Ph.D., Professor of Glyco-Oncology at the university. [Palleon Pharmaceuticals] Press Release

CMC Biologics Announces Development and Manufacturing Agreement with Harpoon Therapeutics

CMC ICOS Biologics, Inc. and Harpoon Therapeutics announced that they have entered into an agreement for the development and manufacturing of HPN424, HPN536, and HPN217, representing three TriTAC^™ molecules for the treatment of various human cancers. [CMC ICOS Biologics, Inc.] Press Release

As Foreign Powers Approve Ebola Vaccines, U.S. Drug Makers Lag in Development Pipeline

In the face of the West Africa Ebola crisis, U.S and Canadian government laboratories and a number of companies in Europe raced to test experimental vaccines. A year and a half after that outbreak was declared over, the world has two licensed Ebola vaccines: One was made by scientists in Russia, the other by scientists in China. And what of the vaccines devised in the U.S., Canada, and Europe? They are still meandering through the developmental pipeline. [STAT News] Editorial

Brexit ‘Breakthrough’ Raises Hope — and Questions

British science is expected to benefit from a deal that would allow EU nationals to remain in the country once it leaves the union. [Nature News] Editorial

NEW Gordon Research Conferences: Lymphatics
March 11-16, 2018
Barga, Italy

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Scientist – Immunology (STEMCELL Technologies Inc.)

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Postdoctoral Positions – Immunotherapy (University of Houston)

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Postdoctoral Positions – Cytokines in Immunity, Stem Cells and Tissue Repair (Weill Cornell Medicine)

Postdoctoral Position – Immunology (Ghent University)

Postdoctoral Scientist – Molecular Genetics of Human T Cell Development (Ghent University)

Postdoctoral Fellow – Mucosal Immunology (University of Lorraine)

Postdoctoral Fellow – Mucosal Infections (University of Utah)

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