Human Immunology News Volume 7.29 | Jul 30 2019

TOP STORY

Clonal Replacement of Tumor-Specific T Cells following PD-1 Blockade

The authors performed paired single-cell RNA and T cell receptor sequencing on 79,046 cells from site-matched tumors from patients with basal or squamous cell carcinoma before and after anti-PD-1 therapy. [Nat Med] Abstract

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The Mechanism of Anti-PD-L1 Antibody Efficacy against PD-L1 Negative Tumors Identifies NK Cells Expressing PD-L1 as a Cytolytic Effector

Investigators showed that some tumors can induce PD-L1 on NK cells via AKT signaling, resulting in enhanced NK cell function and preventing cell exhaustion. Anti-PD-L1 monoclonal antibodies directly acted on PD-L1⁺ NK cells against PD-L1 tumors via a p38 pathway. [Cancer Discov] Abstract

Autoimmune Pathways in Mice and Humans Are Blocked by Pharmacological Stabilization of the TYK2 Pseudokinase Domain

Signaling and functional responses in human T_H17, T_H1, B cells, and myeloid cells integral to autoimmunity were blocked by BMS-986165, both in vitro and in vivo in a Phase I clinical trial. [Sci Transl Med] Full Article

IFN-γ Selectively Suppresses a Subset of TLR4-Activated Genes and Enhancers to Potentiate Macrophage Activation

Scientists used combined transcriptomic and epigenomic approaches to find that IFN-γ selectively abrogated LPS-induced feedback and altered macrophage metabolic pathways by suppressing TLR4-mediated gene activation. [Nat Commun] Full Article

Minimal Dosing of Leukocyte Targeting Trail Decreases Triple-Negative Breast Cancer Metastasis following Tumor Resection

Researchers used a liposomal formulation functionalized with the adhesion receptor E-selectin and the apoptosis-inducing ligand tumor necrosis factor-related apoptosis-inducing ligand to reduce metastasis following tumor resection in an aggressive triple-negative breast cancer mouse model. [Sci Adv] Full Article

Epstein-Barr Virus Reprograms Human B Lymphocytes Immediately in the Prelatent Phase of Infection

The authors found that Epstein-Barr virus-infected naïve B lymphocytes undergo a germinal center-like activation and differentiation program within only a few days after infection to emerge with transcriptomic and phenotypic features resembling plasmablasts and early plasma cells. [Proc Natl Acad Sci USA] Full Article

TMEM203 Is a Binding Partner and Regulator of STRING-Mediated Inflammatory Signaling in Macrophages

Using Tmem203 knockout bone marrow-derived macrophages and transient knockdown of TMEM203 in human monocyte-derived macrophages, scientists showed that TMEM203 protein was required for cGAMP-induced STimulator of IFN Genes (STING) activation. [Proc Natl Acad Sci USA] Abstract

Deep Single-Cell RNA Sequencing Data of Individual T Cells from Treatment-Naïve Colorectal Cancer Patients

Using Smart-seq2 protocol, researchers generated an RNA sequencing dataset of 11,138 T cells isolated from peripheral blood, adjacent normal and tumor tissues of 12 colorectal cancer patients, including four with microsatellite instability. [Sci Data] Abstract

Increased Frequency of Activated CD8⁺ T Cell Effectors in Patients with Psoriatic Arthritis

Scientists found increased percentage of CD8⁺ CCR6⁺ T cell effectors expressing CD69 and of IL-17-producing T cells in patients with psoriatic arthritis. [Sci Rep] Full Article

Bruton’s Tyrosine Kinase Is at the Crossroads of Metabolic Adaptation in Primary Malignant Human Lymphocytes

Investigators found that there is crosstalk between Bruton tyrosine kinase (BTK) signaling and bioenergetic stress responses. In primary chronic lymphocytic leukemia lymphocytes, pharmacological interference with mitochondrial ATP synthesis or glucose metabolism affected BTK activity. [Sci Rep] Abstract

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Targeting Metabolism to Regulate Immune Responses in Autoimmunity and Cancer

Targeting metabolism, rather than particular cell types or cytokines, in metabolically demanding processes such as autoimmunity, graft rejection, cancer and uncontrolled inflammation could lead to successful strategies in controlling the pathogenesis of these complex disorders. [Nat Rev Drug Discov] Abstract

Macrophages at CNS Interfaces: Ontogeny and Function in Health and Disease

The segregation and limited regenerative capacity of the CNS necessitate a specialized and tightly regulated resident immune system that continuously guards the CNS against invading pathogens and injury. CNS-associated macrophages are thought to be involved in regulating the fine balance between the proper segregation of the CNS, on the one hand, and the essential exchange between the CNS parenchyma and the periphery, on the other. [Nat Rev Neurosci] Abstract

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Janssen Reports Positive Top-Line Phase III Results for Ponesimod in Adults with Relapsing Multiple Sclerosis

The Janssen Pharmaceutical Companies of Johnson & Johnson announced positive top-line results from the Phase III OPTIMUM study, which evaluated the efficacy and safety of ponesimod compared to Aubagio^® in adults with relapsing multiple sclerosis. [The Janssen Pharmaceutical Companies] Press Release

ImaginAb Initiates Phase II Clinical Trial at a World-Leading Cancer Center

ImaginAb Inc. announced it has initiated its Phase II clinical trial of its lead product, CD8 tracer ⁸⁹Zr-Df-IAB22M2C. ⁸⁹Zr-Df-IAB22M2C is a first in class imaging agent that visualizes the immune system using non-invasive, whole-body in vivo PET imaging of CD8 T cells. [ImaginAb Inc.] Press Release

Principia Announces Update to Ongoing Phase II Clinical Trial in Patients with ITP

Principia Biopharma Inc. announced updates to its immune thrombocytopenia (ITP) program for PRN1008. [Principia Biopharma Inc.] Press Release

Adaptimmune Starts SPEARHEAD-1 Trial with ADP-A2M4 SPEAR T Cells for Patients with Synovial Sarcoma or MRCLS

Adaptimmune Therapeutics plc has started its SPEARHEAD-1 trial with ADP-A2M4 SPEAR T cells for patients with synovial sarcoma or myxoid/round cell liposarcoma (MRCLS). [Adaptimmune Therapeutics] Press Release

Trump Administration Releases Details on Fetal Tissue Restrictions

The National Institutes of Health detailed how President Donald Trump’s administration will implement restrictions it announced in June on the use of human fetal tissue in research. The policy doesn’t kick in immediately, meaning grant applications already in the pipeline at NIH won’t be affected. But starting in late September, scientists applying for grants will need to explain in detail why they need to use fetal tissue and how it will be obtained. [ScienceInsider] Editorial

Medical Journal Editors Expect Authors to Disclose Conflicts of Interest—But Don’t Disclose Their Own

Virtually all top medical journals require authors to disclose potential conflicts of interest, but few- just 12%- apply that same medicine to their own editors by publicly disclosing editors’ financial ties to industry, a study has found. [ScienceInsider] Editorial

UK Prime Minister Boris Johnson’s Hardline Brexit Stance Stokes Fears for Scientists

Boris Johnson, a charismatic and incautious politician with scant public views on science, became U.K. prime minister last week. He immediately packed his Cabinet with ministers pledging to exit the European Union by a 31 October deadline, even without a deal in place for an amicable divorce—the “no-deal Brexit” that economists predict would cause a recession and scientists say would cause additional hardships for research. [ScienceInsider] Editorial

NEW Cell Symposia: Neuro-Immune Axis: Reciprocal Regulation in Development, Health, and Disease
September 22-24, 2019
Long Beach, California, United States

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