Human Immunology News Volume 7.34 | Sep 3 2019

TOP STORY

Single-Cell Analysis of Crohn’s Disease Lesions Identifies a Pathogenic Cellular Module Associated with Resistance to Anti-TNF Therapy

The authors found that a subset of patients expressed a unique cellular module in inflamed tissues that consisted of IgG plasma cells, inflammatory mononuclear phagocytes, activated T cells, and stromal cells, which they named the GIMATS module. Analysis of ligand-receptor interaction pairs identified a distinct network connectivity that likely drives the GIMATS module. [Cell] Abstract | Graphical Abstract

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Enhanced CAR T Cell Expansion and Prolonged Persistence in Pediatric Patients with ALL Treated with a Low-Affinity CD19 CAR

CD19 chimeric antigen receptor (CAR) T cells showed increased proliferation and cytotoxicity in vitro and had enhanced proliferative and in vivo antitumor activity compared with FMC63 CAR T cells. [Nat Med] Abstract

A Molecular Signature in Blood Reveals a Role for p53 in Regulating Malaria-Induced Inflammation

By integrating whole-blood transcriptomics, flow-cytometric analysis, and plasma cytokine and antibody profiles, researchers demonstrated that a pre-infection signature of B cell enrichment, upregulation of T helper type 1 (Th1) and Th2 cell-associated pathways, including interferon responses, and p53 activation associated with control of malarial fever and coordinated with Plasmodium falciparum-specific immunoglobulin G and Fc receptor activation to control parasitemia. [Immunity] Full Article | Graphical Abstract

Single-Cell Analysis of Human Mononuclear Phagocytes Reveals Subset-Defining Markers and Identifies Circulating Inflammatory Dendritic Cells

By integrating high-dimensional single-cell protein and RNA expression data, investigators identified distinct markers to delineate monocytes from conventional DC2 (cDC2s). Using CD88 and CD89 for monocytes and HLA-DQ and FcεRIα for cDC2s they allowed for their specific identification in blood and tissues. [Immunity] Abstract | Graphical Abstract

N6-Methyladenosine Modification Controls Circular RNA Immunity

Researchers showed that N6-methyladenosine (m⁶A) RNA modification on human circRNAs inhibited innate immunity. Foreign circRNAs were potent adjuvants to induce antigen-specific T cell activation, antibody production, and anti-tumor immunity in vivo, and m⁶A modification abrogated immune gene activation and adjuvant activity. [Mol Cell] Abstract | Graphical Abstract

Heterogeneity of Human Bone Marrow and Blood Natural Killer Cells Defined by Single-Cell Transcriptome

Using single-cell RNA-sequencing technology, the authors identified distinct natural killer populations in human bone marrow and blood, including one population expressing higher levels of immediate early genes indicative of a homeostatic activation. [Nat Commun] Full Article

PI3K-p110δ Contributes to Antibody Responses by Macrophages in Chronic Lymphocytic Leukemia

Researchers demonstrated that the class I phosphoinositide 3-kinase (PI3K) catalytic subunit p110δ was essential for chronic lymphocytic leukemia-derived macrophages to respond to therapeutic antibodies. Inhibition of p110δ in the macrophages reduced FcγR-mediated antibody immune responses. [Leukemia] Abstract

Targeting Tryptophan Catabolic Kynurenine Pathway Enhances Antitumor Immunity and Cytotoxicity in Multiple Myeloma

Using coculture models of patient autologous plasmacytoid dendritic (pDCs)-T-NK-multiple myeloma (MM) cells, scientists showed that pharmacological blockade of kynurenine-3-monooxygenase activated pDCs and triggers both MM-specific cytotoxic T-cell lymphocytes and NK cells cytolytic activity against tumor cells. [Leukemia] Abstract

Neutrophils Promote Tumor Resistance to Radiation Therapy

Investigators showed that elevated neutrophil levels are associated with poor local control and survival in cervical cancer patients treated with definitive chemoradiation. [Proc Natl Acad Sci USA] Abstract

Mass Cytometry Dissects T Cell Heterogeneity in the Immune Tumor Microenvironment of Common Dysproteinemias at Diagnosis and after First Line Therapies

The authors found that AL amyloidosis had a distinct immune tumor microenvironment compared to other dysproteinemias with higher myeloid and “innate-like” T cell subset infiltration. [Blood Cancer J] Abstract

Sensitive Detection and Analysis of Neoantigen-Specific T Cell Populations from Tumors and Blood

Scientists describe a sensitive method for the enumeration and isolation of neoantigen-specific CD8⁺ T cells from small samples of patient tumor or blood. The method relies on magnetic nanoparticles that present neoantigen-loaded major histocompatibility complex tetramers at high avidity by barcoded DNA linkers. [Cell Rep] Full Article | Graphical Abstract

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Dendritic Cells in Cancer Immunology and Immunotherapy

The authors outline how different dendritic cell subsets influence immunity and tolerance in cancer settings and discuss the implications for both established cancer treatments and novel immunotherapy strategies. [Nat Rev Immunol] Abstract

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Celgene, Immatics Launch Up-to-$1.5B+ Cancer T Cell Collaboration

Celgene will partner with Immatics Biotechnologies to develop novel adoptive cell therapies against multiple cancers, through a collaboration that could generate more than $1.5 billion for the German T cell immunotherapy developer—and further expand Celgene’s oncology pipeline in advance of its planned $74 billion acquisition by Bristol-Myers Squibb. [Celgene (Genetic Engineering & Biotechnology News)] Press Release

Concert Pharmaceuticals Reports Positive CTP-543 Results from Phase II Alopecia Areata Trial

Concert Pharmaceuticals, Inc. announced final topline results from its recently completed dose-ranging Phase II trial evaluating its investigational medicine CTP-543 in patients with moderate-to-severe alopecia areata. [Concert Pharmaceuticals] Press Release

Fate Therapeutics Announces FDA Clearance of IND Application for FT596 Off-the-Shelf, iPSC-derived CAR NK Cell Cancer Immunotherapy

Fate Therapeutics, Inc. announced that the FDA has cleared the company’s Investigational New Drug (IND) application for FT596, the company’s first off-the-shelf chimeric antigen receptor (CAR) natural killer (NK) cell cancer immunotherapy which targets multiple tumor-associated antigens. [Fate Therapeutics, Inc.] Press Release

CARsgen Therapeutics Receives US FDA Orphan Drug Designation for Fully Human Anti-BCMA (B Cell Maturation Antigen) Autologous Chimeric Antigen Receptor (CAR) T Cells for the Treatment of Multiple Myeloma

CARsgen Therapeutics Inc. announced the FDA has granted orphan drug designation to its investigational CAR-T cell therapy fully human anti-BCMA autologous CAR T Cells for the treatment of multiple myeloma. [CARsgen Therapeutics Inc.] Press Release

Keck Foundation Awards Tulane University $1 Million to Study Why Women Have Stronger Immune Systems than Men

Do women have an extra line of defense in their immune systems that gives them an advantage over men in fighting infections? That’s one of the questions Tulane University researchers hope to answer using a $1 million grant from the W. M. Keck Foundation to study how sex differences shape disparate immune responses in men and women. [Tulane University] Press Release

As Hurricane Dorian Bears Down, Researchers Get Ready

For the fourth consecutive year, scientists in Florida are preparing for a major hurricane, laying down sandbags and boarding up windows at research facilities along the state’s Atlantic coast. [ScienceInsider] Editorial

Foreign Interference under the Spotlight at Australian Universities

The Australian government says it will establish an expert committee to detect and respond to cyberattacks, intellectual-property theft and other strikes against universities by foreign governments or groups. The move comes amid growing concerns from some politicians and academics about foreign influence at Australian campuses. [Nature News] Editorial

NEW 11^th International Forum on Rheumatoid Arthritis
September 25-27, 2019
Washington, DC, United States

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Position – Stem Cell Biology and Immunology (Columbia University)

Research Technologist (STEMCELL Technologies Inc.)

Scientific Communications Coordinator (STEMCELL Technologies Inc.)

Scientist – Human Immunology (STEMCELL Technologies Inc.)

Research Associate – Immune Cell Culture (STEMCELL Technologies Inc.)

Postdoctoral Research Associate – Autoimmune Diseases (Benaroya Research Institute)

Senior Scientific Researcher – Inflammatory Diseases (Genentech, Inc.)

Postdoctoral Position – Immunogenic Cell Death (University Hospital of Cologne)

Research Assistant – Immunology (MD Anderson Cancer Center)

Postdoctoral Position – Immunology (BioMed X Innovation Center)

Preclinical Scientist – Immunology (MiroBio)

Postdoctoral Position – Immunology of Enteric Infections (University of Utah)

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