Human Immunology News Volume 7.44 | Nov 12 2019

TOP STORY

Clonally Expanded T Cells Reveal Immunogenicity of Rhabdoid Tumors

Comprehensive evaluation of the immune infiltrates of human and mice rhabdoid tumors, including immunohistochemistry, bulk RNA sequencing and DNA methylation profiling studies showed a high rate of tumors infiltrated by T and myeloid cells. Single-cell RNA and T cell receptor sequencing highlighted the heterogeneity of these cells and revealed therapeutically targetable exhausted effector and clonally expanded tissue resident memory CD8⁺ T subpopulations, likely representing tumor-specific cells. [Cancer Cell] Abstract | Graphical Abstract

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Lactate Buildup at the Site of Chronic Inflammation Promotes Disease by Inducing CD4⁺ T Cell Metabolic Rewiring

Scientists report that lactate accumulation in the inflamed tissue contributed to the upregulation of the lactate transporter SLC5A12 by human CD4⁺ T cells. SLC5A12-mediated lactate uptake into CD4⁺ T cells induced a reshaping of their effector phenotype, resulting in increased IL17 production via nuclear PKM2/STAT3 and enhanced fatty acid synthesis. [Cell Metab] Full Article | Graphical Abstract

Mass Cytometry Reveals Global Immune Remodeling with Multi-Lineage Hypersensitivity to Type I Interferon in Down Syndrome

Researchers completed a deep mapping of the immune system in adults with Down syndrome using mass cytometry to evaluate 100 immune cell types, which revealed global immune dysregulation consistent with chronic inflammation, including key changes in the myeloid and lymphoid cell compartments. [Cell Rep] Full Article | Graphical Abstract

Sex Differences in the Blood Transcriptome Identify Robust Changes in Immune Cell Proportions with Aging and Influenza Infection

Immune sex expression signature (iSEXS) reflected sex differences in immune cell proportions, with female-associated genes showing higher expression by CD4⁺ T cells and male-associated genes showing higher expression by myeloid cells. Autosomal-iSEXS detected an increase in monocytes with age in females, reflected sex-differential immune cell dynamics during influenza infection, and predicted antibody response in males, but not females. [Cell Rep] Full Article | Graphical Abstract

NK Cell Reconstitution in Pediatric Leukemic Patients after T-Cell-Depleted HLA-Haploidentical Hematopoietic Stem Cell Transplantation followed by the Reinfusion of iCasp9-Modified Donor T Cells

Scientists found donor iCasp9-T lymphocytes did not have a significant influence on natural killer (NK) cell reconstitution, even if they may positively affect the acquisition of target-induced degranulation of CD56^lowCD16^low NK cells in the T-cell-depleted haplo-hematopoietic stem cell transplanted patients. [J Clin Med] Full Article

Effective and Rapid Generation of Functional Neutrophils from Induced Pluripotent Stem Cells Using ETV2-Modified mRNA

The authors describe a rapid efficient serum- and xenogen-free protocol for neutrophil generation, which was based on direct hematoendothelial programming of human induced pluripotent stem cells using ETV2-modified mRNA. [Stem Cell Reports] Full Article

Intracellular K⁺ and Water Content in Human Blood Lymphocytes during Transition from Quiescence to Proliferation

Researchers showed using flame emission assay that a long-term increase in cell K⁺ content per g cell protein was a mandatory factor for transition of quiescent human peripheral blood lymphocytes to proliferation induced by phytohemagglutinin, phorbol ester with ionomycin, and anti-CD3 antibodies with interleukin-2. [Sci Rep] Full Article

Increased CS 83 Expression of CD34-Positive Monocytes in Donors during Peripheral Blood Stem Cell Mobilization in Humans

Investigators analyzed transplant outcomes of 73 patients whose donor’s peripheral blood cells were cryopreserved during mobilization. CD34⁺ monocytes (CD34⁺ mono) were detected more frequently in male donors, while the detection of CD34⁺ mono in donors was not associated with the patient background. [Sci Rep] Full Article

Age-Associated Changes in Human CD4⁺ T Cells Point to Mitochondrial Dysfunction Consequent to Impaired Autophagy

The authors suggest that older age is associated with persistence of dysfunctional mitochondria in CD4⁺ T lymphocytes caused by defective mitochondrial turnover by autophagy, which may trigger chronic inflammation and contribute to the impairment of immune defense in older persons. [Aging (Albany NY)] Full Article

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CD19 Chimeric Antigen Receptor-T Cells in B-Cell Leukemia and Lymphoma: Current Status and Perspectives

Scientists summarize the current available research evidence in this field, with a special focus on the different challenges faced by treating physicians, and provide future perspectives. [Leukemia] Abstract

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Navidea Biopharmaceuticals Announces Preclinical Therapeutic Research Collaboration with IMV Inc. to Explore the Potential Combinatory Effect with Their Platform-Based Immunotherapies

Navidea Biopharmaceuticals, Inc. and IMV Inc. have entered a preclinical research collaboration to explore the potential combinatory effect of their platform-based immunotherapies. [Navidea Biopharmaceuticals, Inc.] Press Release

X4 Pharmaceuticals Receives Breakthrough Therapy Designation from the FDA for Mavorixafor for the Treatment of WHIM Syndrome

X4 Pharmaceuticals, Inc. announced that the FDA has granted Breakthrough Therapy Designation for mavorixafor for the treatment of adult patients with WHIM syndrome, a rare, inherited, primary immunodeficiency disease caused by genetic mutations in the CXCR4 receptor gene. [X4 Pharmaceuticals, Inc.] Press Release

AbCellera Announces the Issuance of Foundational Patent Claims around Microfluidic Screening Assays for Antibody Discovery

AbCellera Biologics Inc. announced that the U.S. Patent and Trademark Office (USPTO) has granted patent no. 10,466,241 titled “Methods for Assaying Cellular Binding Interactions.” [AbCellera Biologics Inc.] Press Release

More South Korean Academics Caught Naming Kids as Co-Authors

The number of South Korean academics accused of naming children as co-authors on research manuscripts — even though the children did not contribute to the research — continues to grow. [Nature News] Editorial

What the Protests and Violence in Chile Mean for Science

As universities shut down, researchers are demonstrating — and meeting with lawmakers to figure out if science can help solve socio-economic inequality. [Nature News] Editorial

E-Cigs and Opioids: The Next FDA Chief Will Face Several Ongoing Crises

Trump has nominated cancer physician Stephen Hahn to lead a food and drug agency in turmoil. [Nature News] Editorial

Why NIH Is Beefing Up Its Data Sharing Rules after 16 Years

The U.S. National Institutes of Health last week released a draft policy that will require all investigators with NIH funding to make their data sets available to colleagues. For the first time, grantees holding any NIH-funded grant—not just those above a $500,000 threshold in direct costs—will need to submit a detailed plan for sharing data, including steps to protect the privacy of research subjects. [ScienceInsider] Editorial

Google Partners with Major U.S. Health System, Gaining Access to Vast Patient Data in the Process

Google has quietly launched a project with one of the nation’s largest nonprofit health systems in which it has gained access to millions of patient records, including names and birth dates, to help deliver more targeted medical treatment. [STAT News] Editorial

NEW Connecting B Cell Biology with Antibody Structure, Function and Applications
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