Human Immunology News Volume 7.39 | Oct 8 2019

TOP STORY

A Quantitative Multivariate Model of Human Dendritic Cell-T Helper Cell Communication

Using human dendritic cell (DC)-T helper (Th) cell communication as a model, scientists measured 36 DC-derived signals and 17 Th cytokines broadly covering Th diversity in 428 observations. They developed a data-driven, computationally validated model capturing 56 already described and 290 potentially novel mechanisms of Th cell specification. [Cell] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

Single-Cell Immune Landscape of Human Atherosclerotic Plaques

Using single-cell proteomic and transcriptomic analyses, researchers uncovered distinct features of both T cells and macrophages in carotid artery plaques of patients with clinically symptomatic disease compared to asymptomatic disease. [Nat Med] Abstract

Spatial Heterogeneity of the T Cell Receptor Repertoire Reflects the Mutational Landscape in Lung Cancer

Investigators examined heterogeneity of the T cell antigen receptor (TCR) repertoire. The number of TCR sequences selectively expanded in tumors varied within and between tumors and correlated with the number of nonsynonymous mutations. [Nat Med] Abstract

Genetic Modification of Primary Human B Cells to Model High-Grade Lymphoma

The authors describe a co-culture system that enabled the ex vivo expansion and viral transduction of primary human germinal center B cells. Incorporation of CRISPR/Cas9 technology enabled high-throughput functional interrogation of genes recurrently mutated in diffuse large B cell lymphoma. [Nat Commun] Full Article

Context-Specific Regulation of Surface and Soluble IL7R Expression by an Autoimmune Risk Allele

Scientists characterized genetic regulation of IL7R at the protein level in healthy individuals, and found that monocyte surface and soluble IL7R (sIL7R) were markedly induced by lipopolysaccharide. In monocytes, both surface IL7R and sIL7R expression strongly associated with allelic carriage of rs6897932, a disease-associated IL7R polymorphism. [Nat Commun] Full Article

Fine Tuning of the DNAM-1/TIGIT/Ligand Axis in Mucosal T Cells and Its Dysregulation in Pediatric Inflammatory Bowel Diseases (IBD)

The authors showed that DNAM-1 and TIGIT displayed a peculiar expression pattern on gut mucosa T-cell populations, in a microenvironment where their shared ligands were physiologically present. [Mucosal Immunol] Abstract

ADP Secreted by Dying Melanoma Cells Mediates Chemotaxis and Chemokine Secretion of Macrophages via the Purinergic Receptor P2Y12

Scientists showed that P2Y12 was an important chemotaxis receptor, which triggered migration of macrophages towards nucleotide-rich, necrotic tumor areas, and modulated the inflammatory environment upon ADP binding. [Cell Death Dis] Full Article

Tumor Cell-Derived Debris and Igg Synergistically Promote Metastasis of Pancreatic Cancer by Inducing Inflammation via Tumor-Associated Macrophages

Investigators showed that M2 macrophage-derived inflammation also existed in pancreatic ductal adenocarcinoma (PDAC). Debris from PDAC cells induced potent IL-1β release by M2 macrophages via TLR4/TRIF/NF-κB signaling, and this effect was further boosted by IgG that was also derived from PDAC cells. [Br J Cancer] Full Article

Differential Modulation of Human Innate Lymphoid Cell (ILC) Subsets by IL-10 and TGF-β

Scientists demonstrated the differential effects of immunoregulatory cytokines IL-10 and TGF-β on activated ILC1 and ILC2 populations ex vivo. [Sci Rep] Full Article

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Harnessing Innate Immunity in Cancer Therapy

New therapies that promote antitumor immunity have been recently developed. Most of these immunomodulatory approaches have focused on enhancing T-cell responses, either by targeting inhibitory pathways with immune checkpoint inhibitors, or by targeting activating pathways, as with chimeric antigen receptor T cells or bispecific antibodies. [Nature] Abstract

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Nektar Therapeutics Announces Initiation of Two Clinical Studies of Novel T Regulatory Cell Stimulator NKTR-358 (LY3471851) in Patients with Psoriasis and Atopic Dermatitis

Nektar Therapeutics announced the initiation of two Phase Ib studies of NKTR-358, a novel T regulatory cell stimulator, one in patients with psoriasis and one in patients with atopic dermatitis. [Nektar Therapeutics] Press Release

Regen BioPharma Successfully Treats Rheumatoid Arthritis Using Cannabidiol (CBD) Based Immune Modulatory Treatments

Regen BioPharma Inc. announced positive data demonstrating that its novel CBD-based therapeutic approach successfully reduces rheumatoid arthritis in an animal model. [Regen BioPharma Inc. (PR Newswire Association LLC.)] Press Release

Ziopharm Oncology Announces FDA Clearance of IND for Rapid Personalized Manufacture of CD19-Specific CAR-T

Ziopharm Oncology, Inc. announced that the FDA has cleared an Investigational New Drug application (IND) for a Phase I clinical trial to evaluate CD19-specific CAR-T, produced using a process termed rapid personalized manufacture, as an investigational treatment for patients with relapsed CD19⁺ leukemias and lymphomas. [Ziopharm Oncology, Inc.] Press Release

Cabaletta Bio Receives IND Clearance from FDA to Initiate First Clinical Trial of DSG3-CAART in Patients with Mucosal Pemphigus Vulgaris

Cabaletta Bio, Inc. announced that it has received clearance of its Investigational New Drug (IND) application from the FDA to initiate a first-in-human clinical trial of desmoglein 3 chimeric autoantibody receptor T cells (DSG3-CAART) in patients with mucosal pemphigus vulgaris to assess the safety and tolerability of DSG3-CAART in these patients. [Cabaletta Bio, Inc.] Press Release

‘More Women Are Being Nominated’: Nobel Academy Head Discusses Diversity

Ahead of this year’s award announcements, Göran Hansson speaks about measures to address the imbalance in gender and ethnicity among winners. [Nature News] Editorial

Biologists Who Decoded How Cells Sense Oxygen Win Medicine Nobel

A trio of researchers has won the 2019 Nobel Prize in Physiology or Medicine for describing how cells sense and respond to changing oxygen levels by switching genes on and off — a discovery that has been key in understanding human diseases such as cancer and anemia. [Nature News] Editorial

There’s No Taboo, No Bad Ideas’: Anyone Can Help Shape European Union’s New €94 Billion Research Program

These encouraging words were spoken at the European Research and Innovation Days, where policy bigwigs working with the European Commission invited the audience to help shape Europe’s next seven-year research funding program, Horizon Europe, set to begin in 2021. Their message: Anyone can help “cocreate” the program’s outlines. [ScienceInsider] Editorial

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