Human Immunology News Volume 6.38 | Sep 25 2018

TOP STORY

T Cells in Patients with Narcolepsy Target Self-Antigens of Hypocretin Neurons

Researchers used sensitive cellular screens and detected hypocretin-specific CD4⁺ T cells in all 19 patients that were tested; T cells specific for tribbles homologue 2—another self-antigen of hypocretin neurons—were found in 8 out of 13 patients. [Nature] Abstract | Press Release

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B-Cell Receptor-Mediated NFATc1 Activation Induces IL-10/STAT3/PD-L1 Signaling in Diffuse Large B-Cell Lymphoma

The authors used proteomic approaches and patient-derived B-cell lymphoma cell lines to investigate mechanisms that regulate PD-L1 expression. They found that PD-L1 expression, particularly in non-germinal center B cell-derived diffuse large B-cell lymphoma, is controlled and regulated by several interactive signaling pathways, including the B-cell receptor and JAK2/STAT3 signaling pathways. [Blood] Abstract

Human Sox4 Facilitates the Development of CXCL13-Producing Helper T Cells in Inflammatory Environments

Researchers showed that Sox4 was a key transcription factor for CXCL13 production in human CD4⁺ T cells under inflammatory conditions. [Nat Commun] Full Article

Acquired Cancer Resistance to Combination Immunotherapy from Transcriptional Loss of Class I HLA

Scientists treated two patients with metastatic Merkel cell carcinoma with autologous Merkel cell polyomavirus specific CD8⁺ T cells and immune-checkpoint inhibitors. In both cases, dramatic remissions were associated with dense infiltration of activated CD8⁺s into the regressing tumors. [Nat Commun] Full Article | Press Release

RIPK1 Is a Critical Modulator of Both Tonic and TLR-Responsive Inflammatory and Cell Death Pathways in Human Macrophage Differentiation

Using a well-established macrophage differentiation protocol, knock-out of RIPK1 did not block the differentiation of induced pluripotent stem cell (iPSC)-derived macrophages, which displayed a similar phenotype to WT human iPSC-derived macrophages. [Cell Death Dis] Full Article

A Novel Human IL-2 Mutein with Minimal Systemic Toxicity Exerts Greater Antitumor Efficacy than Wild-Type IL-2

FSD13 had a greater ability than wild-type IL-2 in stimulating CD4⁺ T, CD8⁺ T, and NK cell proliferation, enhancing the expression of CD69, CD183, CD44, and CD54 in these cells, and triggering cancer cell apoptosis. [Cell Death Dis] Full Article

Protein Profile of Blood Monocytes Is Altered in HTLV-1 Infected Patients: Implications for HAM/TSP Disease

Monocytes from human T-cell lymphotropic virus type-1 (HTLV-1)-infected individuals exhibited important functional differences when compared to cells from uninfected donors. Using proteomic shot gun strategy, performed by nanoACQUITY-UPLC system, the authors analyzed monocytes isolated from peripheral blood of asymptomatic carriers, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and uninfected individuals. [Sci Rep] Full Article

VSIG-3 as a Ligand of VISTA Inhibits Human T Cell Function

Investigators report that VSIG-3/IGSF11 is a ligand of the B7 family member VISTA/PD-1H and inhibits human T cell functions through a novel VSIG-3/VISTA pathway. [Immunology] Abstract

Impact of Human Sepsis on CCCTC-Binding Factor Associated Monocyte Transcriptional Response of Major Histocompatibility Complex II Components

Compared to healthy controls, CD14⁺⁺ CD16^–monocytes from septic patients with immune suppression displayed an increased binding of CCCTC-binding factor within the MHC-II locus combined with decreased transcription of class II major histocompatibility complex transactivator CIITA gene. [PLoS One] Full Article

G-Quadruplex-Forming Oligodeoxyribonucleotides Activate Leukotriene Synthesis in Human Neutrophils

Researchers showed that exogenous G-quadruplex-forming oligodeoxyribonucleotides significantly enhanced 5-lipoxygenase metabolite formation in human neutrophils exposed to Salmonella typhimurium bacteria. [J Biomol Struct Dyn] Abstract

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Modulation of Three Key Innate Immune Pathways for the Most Common Retinal Degenerative Diseases

The authors highlight the role of three key immune pathways in the pathophysiology of major retinal degenerative diseases including diabetic retinopathy, age-related macular degeneration, and rare retinal dystrophies. [EMBO Mol Med] Full Article

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First Neuroblastoma Patient Successfully Dosed with Innovative CAR Therapy Utilizing Natural Killer T Cells (CAR-NKT)

Cell Medica announced the treatment of the first patient worldwide to receive CMD-501, an autologous CAR-NKT therapy targeting pediatric neuroblastoma. [Cell Medica] Press Release

AIVITA Biomedical Announces Treatment of First Patient in Phase II Ovarian Cancer Trial

AIVITA Biomedical announced that it has dosed its first of 10 patients currently enrolled as part of its Phase II trial in patients with advanced ovarian cancer. The trial is designed to investigate AIVITA Biomedical’s patient-specific cancer treatment consisting of autologous dendritic cells loaded with autologous antigens from the patient’s tumor-initiating cells. [AIVITA Biomedical] Press Release

Abzena Announces a Research and Licence Agreement with Tmunity Therapeutics, a T Cell Engineering Company

Abzena, plc has signed an antibody humanization agreement with Tmunity Therapeutics, a clinical stage T cell therapy company and a leader in the development of new chimeric antigen receptor T cell therapies for the treatment of solid and hematological cancers. [Abzena, plc] Press Release

Regen BioPharma, Inc. Reports Activation of Immune Cells by Its NR2F6 Small Molecule Inhibitors

Regen BioPharma Inc. reported its researchers have identified a series of small molecule drugs that inhibit NR2F6 and also activate human immune cells ex-vivo. [Regen BioPharma Inc. (PR Newswire Association LLC.)] Press Release

Trump Administration Launches Review of Scientific Research Involving Fetal Tissue

The Trump administration has launched a comprehensive review of all research that involves fetal tissue, reopening an issue that has galvanized anti-abortion activists but worried scientists who fear their work could be under threat. [STAT News] Editorial

Portrayals of Female STEM Characters in TV and Film Haven’t Improved in 10 Years

The Lyda Hill Foundation, in partnership with Geena Davis’s Institute on Gender in Media at Mount Saint Mary’s University, released an extensive research report on the portrayals of female characters in science, technology, engineering and math in television and film. “Portray Her: Representations of Women STEM Characters in Media” shows that entertainment media has a long way to go to improve stereotypes about pursuing STEM careers. [EurekAlert] Editorial

More and More Scientists Are Preregistering Their Studies. Should You?

Preregistration, in its simplest form, is a one-page document answering basic questions such as: What question will be studied? What is the hypothesis? What data will be collected, and how will they be analyzed? In its most rigorous form, a “registered report,” researchers write an entire paper, minus the results and discussion, and submit it for peer review at a journal, which decides whether to accept it in principle. [ScienceInsider] Editorial

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