Human Immunology News Volume 7.48 | Dec 10 2019

TOP STORY

Human Tolerogenic Dendritic Cells Regulate Immune Responses through Lactate Synthesis

In vivo, autologous tolerogenic dendritic cells promoted elevated levels of circulating lactate and delayed graft-versus-host disease by reducing T cell proliferative capacity. [Cell Metab] Abstract | Graphical Abstract

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The Human Tissue-Resident CCR5⁺ T Cell Compartment Maintains Protective and Functional Properties during Inflammation

The authors found that 65% of the CD4 tissue-resident memory T (T_RM) cell compartment expressed CCR5. These CCR5⁺ T_RM cells were enriched in and near the epithelial layer and not only limited to T_H1-type cells but also contained a large T_H17-producing and a stable regulatory T cell population. [Sci Transl Med] Abstract

Challenging Immunodominance of Influenza-Specific CD8⁺ T Cell Responses Restricted by the Risk-Associated HLA-A*68:01 Allomorph

Scientists elucidated the HLA-A*68:01⁺CD8⁺ T cell response directed toward an extended influenza-derived nucleoprotein peptide and showed that only ~35% individuals had immunodominant A68/NP145⁺CD8⁺ T cell responses. [Nat Commun] Full Article

Leptin Induces TNFα-Dependent Inflammation in Acquired Generalized Lipodystrophy and Combined Crohn’s Disease

Investigators showed that recombinant N-methionylleptin exerted diverse pro-inflammatory effects on immune cell differentiation and function, including the metabolic reprogramming of immune cells and the induction of TNFα, ultimately aggravating Crohn’s disease in the acquired generalized lipodystrophy and Crohn’s disease patient, which could be reversed by anti-TNFα therapy. [Nat Commun] Full Article

Features of Non-Activation Dendritic State and Immune Deficiency in Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

To identify disease-specific molecular features of BPDCN, scientists profiled bone marrow, peripheral blood, and serum samples from primary patient samples using an in-house hematologic malignancy panel, transcriptome microarray, and serum multiplex immunoassays. [Blood Cancer J] Full Article

Type I IFN Ineffectively Activates Neonatal Dendritic Cells Limiting Respiratory Antiviral T-Cell Responses

Investigators discovered that during infection neonatal conventional neonatal dendritic cells presenting viral antigen were unable to upregulate costimulatory molecules in response to type I interferons (IFN-I), contributing to poor antiviral T-cell responses. [Mucosal Immunol] Abstract

BRD4 Promotes Tumor Progression and NF-κB/CCL2-Dependent Tumor-Associated Macrophage Recruitment in GIST

BRD4 enhanced CCL2 expression by activating the NF-κB signaling pathway. Furthermore, this CCL2 upregulation caused recruitment of macrophages into the tumor leading to tumor growth. [Cell Death Dis] Full Article

Eugenol Prevents fMLF-Induced Superoxide Anion Production in Human Neutrophils by Inhibiting ERK1/2 Signaling Pathway and p47phox Phosphorylation

Researchers showed that eugenol decreased the phosphorylation of p47phox onSer-345 and Ser-328, the translocation of p47phox to the membranes and the phosphorylation of Raf, MEK1/2 and ERK1/2 proteins. [Sci Rep] Full Article

Adult Peripheral Blood and Umbilical Cord Blood NK Cells Are Good Sources for Effective CAR Therapy against CD19 Positive Leukemic Cells

Adult peripheral blood chimeric antigen receptor (CAR)-NK cells were slightly better at killing CD19 presenting target cells and cord blood NK cells were easier to stimulate and they had more stable number from donor to donor. [Sci Rep] Full Article

T Cell-Derived Interferon-γ Programs Stem Cell Death in Immune-Mediated Intestinal Damage

Investigators found that stem cell compartment injury was a shared feature of both alloreactive and autoreactive intestinal immunopathology, reducing intestinal stem cells and impairing their recovery in T cell-mediated injury models. [Sci Immunol] Full Article

More Than One Antibody of Individual B Cells Revealed by Single-Cell Immune Profiling

Researchers revealed an unprecedented presence of multi-Ig specificity in some single B cells, implying regulation of Ig gene rearrangement and class switching that differs from the classical mechanisms of both the “one cell — one antibody” rule and class-switch recombination. [Cell Discov] Full Article

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T_reg Cell-Based Therapies: Challenges and Perspectives

Scientists discuss the biology of T_reg cells and describe new efforts in T_reg cell engineering to enhance specificity, stability, functional activity and delivery. [Nat Rev Immunol] Abstract

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Bristol-Myers Squibb and bluebird bio Announce Positive Top-Line Results from the Pivotal Phase II KarMMa Study of Ide-cel in Relapsed and Refractory Multiple Myeloma

Bristol-Myers Squibb Company and bluebird bio, Inc. announced positive top-line results from KarMMa, a pivotal, open-label, single arm, multicenter, Phase II study of idecabtagene vicleucel. [Bristol-Myers Squibb Company] Press Release

HIZENTRA^® (Immune Globulin Subcutaneous [Human] 20% Liquid) Receives Orphan-Drug Exclusivity for the Treatment of Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

CSL Behring announced that Hizentra received orphan-drug exclusivity from the FDA for the treatment of adult patients with CIDP as maintenance therapy to prevent relapse of neuromuscular disability and impairment. [CSL Behring] Press Release

CASI Pharmaceuticals Announces China NMPA Approval Of CNCT19 (CD19 CAR-T) Clinical Trial Applications

CASI Pharmaceuticals, Inc. announced that the China National Medical Product Administration, has approved the clinical trial applications for CNCT19 in relapsed/refractory B-cell acute lymphoblastic leukemia and relapsed/refractory B-cell non-Hodgkin lymphoma. [CASI Pharmaceuticals, Inc.] Press Release

Merck and Sanofi Buy Smaller Cancer Drug Firms at Big Premiums, Fueling Investor Excitement

The drug giants Merck and Sanofi each said they would acquire a smaller drug maker for more than $2 billion – in each case, more than double the smaller company’s market capitalization – cheering investors about large companies’ appetite to execute buyouts in the biotechnology sector. [STAT News] Editorial

House Republicans Fuel Capitol Hill Chaos with Competing Drug Pricing Bill

Republicans are set to accelerate Capitol Hill’s drug pricing chaos with a new proposal to lower the cost of prescription medicines, according to a summary document obtained by STAT. [STAT News] Editorial

NEW Keystone Symposia: Noncoding RNAs – Mechanism, Function and Therapies
January 12-16, 2020
Whistler, British Columbia, Canada

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NEW Postdoctoral Fellows – Microbiota in Immune Development (Institut Pasteur of Shanghai)

Scientist – Human Immunology (STEMCELL Technologies Inc.)

Postdoctoral Research Associate – Vaccines and Immunotherapies (University of Montana)

Postdoctoral Fellow – Autoimmune Pathogenesis (Oklahoma Medical Research Foundation)

Post-Doctoral Fellow – Cancer Immunology/Bioengineering (West Virginia University)

Postdoctoral Fellow – Infection, Inflammation and Immunology (The Boston University Pulmonary Center)

Group Leader Position – Immunology (Research Institute of Molecular Pathology)

Postdoctoral Position – B Cells (Institut Necker Enfants Malades)

Director of Operations – Immunopathogenesis (The Immunotherapy Assessment Core)

Postdoctoral Positions – Immunotherapies (Indiana University School of Medicine)

PhD Studentship – Melanoma (Cancer Research UK Manchester Institute)

Postdoctoral Position – Blood Cancer Immunology (University Children’s Hospital Basel)

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