Human Immunology News Volume 6.41 | Oct 16 2018

TOP STORY

IRE1α-XBP1 Controls T Cell Function in Ovarian Cancer by Regulating Mitochondrial Activity

In T cells isolated from specimens collected from patients with ovarian cancer, upregulation of XBP1 was associated with decreased infiltration of T cells into tumors and with reduced IFNG mRNA expression. [Nature] Abstract | Press Release

(Ranked by impact factor of the journal)

GDP-_L-Fucose Synthase Is a CD4⁺ T Cell-Specific Autoantigen in DRB3*02:02 Patients with Multiple Sclerosis

By using a brain-infiltrating CD4⁺ T cell clone that is clonally expanded in multiple sclerosis brain lesions and a systematic approach for the identification of its target antigens, positional scanning peptide libraries in combination with biometrical analysis, scientists identified guanosine diphosphate (GDP)-_L-fucose synthase as an autoantigen that was recognized by cerebrospinal fluid-infiltrating CD4⁺ T cells from HLA-DRB3*-positive patients. [Sci Transl Med] Abstract | Press Release

Cycling CD4⁺ T Cells in HIV-Infected Immune Nonresponders Have Mitochondrial Dysfunction

Scientists showed that cells with the phenotype and transcriptional profile of Tregs were enriched among cycling cells in health and in HIV infection. Yet there were diminished frequencies and numbers of Tregs among cycling CD4⁺ T cells in immune nonresponders (INRs), and cycling CD4⁺ T cells from INR subjects displayed transcriptional profiles associated with the impaired development and maintenance of functional Tregs. [J Clin Invest] Full Article

Complement Receptor CD46 Co-Stimulates Optimal Human CD8⁺ T Cell Effector Function via Fatty Acid Metabolism

Researchers showed, using cytotoxic CD8⁺ T cells (CTLs) from patients with CD46 deficiency or with constitutively-active NLRP3, that CD46 delivers co-stimulatory signals for optimal CTL activity by augmenting nutrient-influx and fatty acid synthesis. [Nat Commun] Full Article

Human Breast Tumor-Infiltrating CD8⁺ T Cells Retain Polyfunctionality Despite PD-1 Expression

Investigators interrogated CD8⁺ tumor-infiltrating lymphocytes (TILs) from human breast and melanoma tumors to explore their functional state. Despite expression of exhaustion hallmarks, such as PD-1 expression, human breast tumor CD8⁺ TILs retained robust capacity for production of effector cytokines and degranulation capacity. [Nat Commun] Full Article

Sex Influences SAMHD1 Activity and Susceptibility to HIV-1 in Primary Human Macrophages

Scientists explored whether sex affects HIV-1 infectivity of primary human macrophages and CD4⁺ T cells in vitro. They found that macrophages derived from female donors were less susceptible to HIV-1 infection than those derived from males. [J Infect Dis] Abstract

High Levels of Circulating GM-CSF⁺CD4⁺ T Cells Are Predictive of Poor Outcomes in Sepsis Patients: A Prospective Cohort Study

The authors report peripheral changes in granulocyte colony-stimulating factor (GM-CSF)-producing CD4⁺ T cells in septic patients and the possible underlying mechanism by which GM-CSF influences the outcome of sepsis. [Cell Mol Immunol] Abstract

Increased CD3⁺ T Cells with a Low FOXP3⁺/CD8⁺ T Cell Ratio Can Predict Anti-PD-1 Therapeutic Response in Non-Small Cell Lung Cancer Patients

To determine whether tumor microenvironments affect the clinical response to anti-PD-1 therapy in non-small cell lung cancer, researchers investigated the expression level of PD-L1 and tumor infiltrating lymphocytes and elucidated their predictive role. [Mod Pathol] Abstract

Evidence for a Direct Link between PAD4-Mediated Citrullination and the Oxidative Burst in Human Neutrophils

The authors report that protein arginine deiminase 4 (PAD4) was physically associated with the cytosolic subunits of the oxidative burst machinery, p47^phox and p67^phox. [Sci Rep] Full Article

Quantitative B-Lymphocyte Deficiency and Increased TCRγδ T-Lymphocytes in Acute Infectious Spondylodiscitis

In this prospective multicentre study, flow cytometric analysis of T and B-lymphocyte subsets was performed in 35 patients at diagnosis and three months after treatment cessation. [Sci Rep] Full Article

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CAR T-Cells for T-Cell Malignancies: Challenges in Distinguishing between Therapeutic, Normal, and Neoplastic T-Cells

Chimeric antigen receptor (CAR) T-cells targeting CD19 demonstrated remarkable efficacy for the treatment of B-cell malignancies. The development of CAR T-cells against T-cell malignancies appears more challenging due to the similarities between the therapeutic, normal and malignant T-cells. [Leukemia] Abstract

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Celyad Announces Exclusive Agreement for Horizon Discovery’s shRNA Platform to Develop Next-Generation Allogeneic CAR-T Therapies

Celyad announced an exclusive agreement with Horizon Discovery Group plc for the use of its shRNA technology to generate Celyad’s second non-gene-edited allogeneic platform. [Celyad] Press Release

SQZ Biotech Expands Cell Therapy Partnership with Roche to Develop Antigen Presenting Cells for Immune-Oncology

SQZ Biotechnologies announced the expansion of its collaboration with Roche in cellular therapy. The expanded partnership furthers the synergistic combination of SQZ’s innovation and expertise in cell therapy with Roche’s cancer immunotherapy expertise. [SQZ Biotechnologies] Press Release

Applied DNA Subsidiary LineaRx Licenses CAR T Drug Candidate and Initiates Pre-Clinical Development of Non-Viral, Plasmid-Free CAR T Manufacturing Platform

Applied DNA Sciences Inc. announced that LineaRx, Inc. has initiated pre-clinical development of a non-viral, plasmid-free chimeric antigen receptor modified T cell (CAR T) manufacturing platform which will be made available to CAR T developers worldwide. [Applied DNA Sciences Inc.] Press Release

Athenex and Xiangxue Life Sciences Announce Preliminary Results of Patients Receiving T-Cell Receptor Affinity Enhancing Specific T-Cell Therapy (TAEST) Showed Encouraging Positive Clinical Signals

Athenex, Inc. announced that preliminary results of pilot studies in China in which patients received T-cell receptor affinity enhancing specific T-cell therapy showed encouraging positive clinical signals in terms of efficacy and safety. [Athenex, Inc.] Press Release

China Awaits Controversial Blacklist of ‘Poor Quality’ Journals

A proposal by the Chinese government to create a national blacklist of journals is creating much debate among the country’s scientists, who are still waiting for the list to be revealed, five months after the plan to create it was announced. [Nature News] Editorial

Journal Blacklists: Show Your Working

This January, China was reported as overtaking the United States to become the largest producer of scientific papers. There is one major caveat, however, which consoles those who worry about China’s rise and worries those who cheer for it: a lot of those Chinese publications are of poor quality. [Nature News] Editorial

UCSF Settles Sexual Harassment Suit Involving Star Researcher

The University of California, San Francisco, has agreed to pay a former postdoc $150,000 to settle a sexual harassment lawsuit involving a prominent tobacco researcher on its faculty. [STAT News] Editorial

NEW AACR: Targeting RAS-Driven Cancers
December 9-12, 2018
San Diego, California, United States

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NEW PhD Position – Antigen Presentation and Immune Regulation (Erasmus MC)

Postdoctoral Fellow – Statistical Geneticist/Computational Biologist (Wellcome Sanger Institute)

Postdoctoral Researcher – Autophagy and Aging (University of Oxford)

Research Assistant II – Immunology (Baylor College of Medicine)

Faculty Position – Immunology (Benaroya Research Institute)

Faculty Position – Systems Immunology (Benaroya Research Institute)

Project Leader – Immuno-Oncology (CELLECTIS Inc.)

Postdoctoral Fellowship – Immunology (University of Nantes)

Postdoctoral Fellow – Foxp3+ T-Regulatory in Autoimmunity and Transplantation (Children’s Hospital of Philadelphia)

Postdoctoral Associates – Cancer Immunology and/or Bioinformatics (Emory University)

Institute Group Leader – Lymphocyte Biology (MD Anderson Cancer Center)

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