Human Immunology News Volume 8.02 | Jan 21 2020

TOP STORY

B Cells and Tertiary Lymphoid Structures Promote Immunotherapy Response

The authors performed bulk RNA sequencing and found that B cell markers were the most differentially expressed genes in the tumors of responders versus non-responders. Their findings were corroborated using a computational method to estimate the immune and stromal composition in this and two other immune checkpoint blockade-treated cohorts. [Nature] Abstract

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Signaling Through the Inhibitory FC Receptor FcγRIIB Induces CD8⁺ T Cell Apoptosis to Limit T Cell Immunity

Fgl2 induced caspase-3/7-mediated apoptosis in Fcgr2b⁺, but not Fcgr2b^-/-, CD8⁺ T cells. Increased expression of FcγRIIB correlated with freedom from rejection following withdrawal from immunosuppression in a clinical trial of kidney transplant recipients. [Immunity] Abstract | Graphical Abstract

Ionizable Lipid Nanoparticle Mediated mRNA Delivery for Human CAR T Cell Engineering

Ionizable lipids nanoparticles (LNPs) were designed for ex vivo mRNA delivery to human T cells. A library of 24 ionizable lipids was synthesized, formulated into LNPs, and screened for luciferase mRNA delivery to Jurkat cells, revealing seven formulations capable of enhanced mRNA delivery over lipofectamine. [Nano Lett] Abstract

Distinctive Phenotypes and Functions of Innate Lymphoid Cells in Human Decidua during Early Pregnancy

Using mass cytometry, researchers characterized five main decidual innate lymphoid cell) subsets: decidual NK cells (dNK)1–3, ILC3s and proliferating NK cells. Following stimulation, dNK2 and dNK3 produce more chemokines than dNK1 including XCL1 which could act on both maternal dendritic cells and fetal extravillous trophoblasts. [Nat Commun] Full Article

Sensing of HIV-1 by TLR8 Activates Human T Cells and Reverses Latency

Investigators showed that synthetic ligands of TLR8 boosted T cell receptor signaling, resulting in increased cytokine production and upregulation of surface activation markers. Adjuvant TLR8 stimulation, but not TLR7 or TLR9, further promoted T helper cell differentiation towards Th1 and Th17. [Nat Commun] Full Article

Development of a Protein-Based System for Transient Epigenetic Repression of Immune Checkpoint Molecule and Enhancement of Antitumor Activity of Natural Killer Cells

A protein-based genome modulator system is composed of a transcription activator-like effector, DNA methyltransferase and a newly identified potent cell-penetrating peptide with nuclear-trafficking property named NTP. TALE was designed to target the promoter region of the programmed cell death-1 (PD-1) gene. After culturing human NK cells in the presence of NTP-GM protein, they examined endogenous PD-1 expression and anti-tumor activity of the treated cells. [Br J Cancer] Abstract

A Novel Cytological Model of B-Cell/Macrophage Biphenotypic Cell Hodgkin Lymphoma in Ganp-Transgenic Mice

The authors investigated whether the lymphoid tumor developed in Ig-ganpTg mice exhibit biphenotypic characteristics of B cells/macrophages that correspond to human Hodgkin lymphoma (HL). They demonstrated GANP overexpression in human HL cells and found that it may regulate transdifferentiation between B cells and macrophages. [Cancers] Abstract | Download Full Article

The Adaptive and Innate Immune Cell Landscape of Uterine Leiomyosarcomas

Investigators analyzed the inflammatory infiltrate of 21 such cases in high-dimensional, single cell phenotyping on routinely processed tissue. T-lymphoid cells displayed a composite phenotype common to all tumors, suggestive of antigen-exposure, acute and chronic exhaustion. [Sci Rep] Full Article

Immune Gene Signatures for Predicting Durable Clinical Benefit of Anti-PD-1 Immunotherapy in Patients with Non-Small Cell Lung Cancer

Researchers used multipanel markers to predict the response to immune checkpoint inhibitors (ICIs) by characterizing gene expression signatures or individual genes in patients who showed durable clinical benefit to ICIs. Twenty-one patients with NSCLC treated with single-agent anti-programmed cell death protein (PD)-1 antibody were analyzed and their clinicopathological characteristics and response to ICIs were characterized. [Sci Rep] Full Article

Role of TLR4 Receptor Complex in the Regulation of the Innate Immune Response by Fibronectin

Scientists evaluated the requirement of the canonical TLR4/MD2/CD14 receptor complex in the regulation of FnIII-1c induced cytokine release. Using dermal fibroblasts and human embryonic kidney cells, they found that all the components of the TLR4/MD2/CD14 complex were required for the release of the fibro-inflammatory cytokine, interleukin 8 in response to both FnIII-1c and the canonical TLR4 ligand, lipopolysaccharide. [Cells] Abstract | Download Full Article

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Human Anti-Tumor Immunity: Insights from Immunotherapy Clinical Trials

The clinical activity of these newer investigational therapies has been mixed, with some therapeutics showing promise but others not exhibiting appreciable efficacy. The authors summarize the results of select recent clinical studies of cancer immunotherapies beyond anti-CTLA-4 and anti-PD(L)1 and discuss how these results are providing new insights into the regulation of human anti-tumor immunity. [Immunity] Abstract

Immune Checkpoint Molecules in Pregnancy: Focus on Regulatory T Cells

Investigators emphasize the potential influence of multiple immune checkpoint molecules, including CTLA-4, PD-1, Tim-3, LAG-3 and TIGIT, either in membrane or soluble form, on the function of decidual and peripheral Regulatory T cells during pregnancy. Additionally, they discuss the promising future of targeting Treg cells via immune checkpoint molecules for pregnancy maintenance and prevention of complicated pregnancies. [Eur J Immunol] Abstract

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Aldeyra Therapeutics Announces First Patient Enrolled in the Phase III INVIGORATE Trial in Allergic Conjunctivitis

Aldeyra Therapeutics, Inc. announced enrollment of the first patient into the Phase III INVIGORATE Trial of topical ocular reproxalap in patients with allergic conjunctivitis. [Aldeyra Therapeutics, Inc.] Press Release

OSE Immunotherapeutics Announces Issuance of a New Patent in Japan for Tedopi^® on Inducing Early T-Lymphocyte Memory Response

OSE Immunotherapeutics announced that the Japanese Patent Office has issued a new patent family related to Tedopi^®, a combination of neoepitopes, protecting the product’s method for inducing early T-lymphocyte memory response for use in the treatment of cancer in HLA-A2 positive patients. [OSE Immunotherapeutics] Press Release

Anokion Announces FDA Clearance of IND Application for Its Lead Program in Celiac Disease

Anokion SA announced that the FDA has accepted its Investigational New Drug (IND) application for KAN-101, the company’s lead antigen-specific drug candidate. Anokion plans to initiate its multi-center Phase I study for KAN-101 in people with celiac disease in the first quarter of 2020. [Anokion SA] Press Release

Campus Attacks by Nationalists and Police Alarm India’s Scientific Community

The attack on one of India’s most prestigious universities sent shock waves around the country and is the latest sign that the political forces tearing apart Indian society are also affecting the country’s academic community. Students at JNU, a liberal bastion, had been on strike for months against both a major hike in student fees and the government’s controversial Citizenship Amendment Act, widely decried as discriminatory against Muslims. [ScienceInsider] Editorial

Moffitt Cancer Center Details Links of Fired Scientists to Chinese Talent Programs

Six Florida cancer researchers who were dismissed last month for hiding their ties to a Chinese medical university appear to have been motivated by simple greed and a disregard for both institutional and federal rules. [ScienceInsider] Editorial

NEW Keystone Symposia: T Cell Memory
March 1-5, 2020
Banff, Alberta, Canada

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NEW Scientist – Immunology (STEMCELL Technologies Inc.)

NEW Research Associate – Human Immunology (STEMCELL Technologies Inc.)

NEW Research Associate – Bioengineering (STEMCELL Technologies Inc.)

Research Scientist – Immuno-Oncology (Ervaxx)

Postdoctoral Position – Tumor Immunology (University Hospital Carl Gustav Carus Dresden)

Chief – Division of Immunology (Boston Children’s Hospital)

Research Assistant Professor – Immunology (The University of Chicago)

Postdoctoral Fellowship – Breast Cancer Immunology and Immunotherapy (The University of Texas Southwestern Medical Center)

Postdoctoral Fellow – Immune Defense and HIV (Massachusetts General Hospital)

Postdoctoral Fellow – Autoimmune Pathogenesis (Oklahoma Medical Research Foundation)

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

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