Human Immunology News Volume 8.12 | Mar 31 2020

TOP STORY

A Conserved Dendritic-Cell Regulatory Program Limits Antitumor Immunity

Using single-cell RNA sequencing in human and mouse non-small-cell lung cancers, researchers identified a cluster of dendritic cells (DCs) that they named ‘mature DCs enriched in immunoregulatory molecules’, owing to their co-expression of immunoregulatory genes and maturation genes. [Nature] Abstract

(Ranked by impact factor of the journal)

Constitutive Activation of RAS/MAPK Pathway Cooperates with Trisomy 21 and Is Therapeutically Exploitable in Down Syndrome B-Cell Leukemia

The authors built the first preclinical cohort of patient-derived xenograft models of Down yndrome-acute lymphoblastic leukemia, comprehensively characterized at the genetic and transcriptomic levels, and provded its suitability for preclinical studies by assessing the efficacy of drug combination between the MEK inhibitor Trametinib and conventional chemotherapy agents. [Clin Cancer Res] Abstract

Rosuvastatin Enhances VSV-G Lentiviral Transduction of Natural Killer Cells via Upregulation of the Low-Density Lipoprotein Receptor

Investigators tested the potential of five statins and five non-statin compounds to increase the low-density lipoprotein-receptor (LDLR) expression, thereby facilitating viral transduction. They found that the transduction efficiency of VSV-G pseudotyped lentivirus was augmented by statins that induced higher LDLR expression. [Mol Ther Methods Clin Dev] Abstract | Full Article | Graphical Abstract

Treatment Response, Survival, Safety, and Predictive Factors to Chimeric Antigen Receptor T Cell Therapy in Chinese Relapsed or Refractory B Cell Acute Lymphoblast Leukemia Patients

Baseline data were collected from patients’ electronic medical records. Patients’ peripheral blood, bone marrow aspirates, and biopsies were obtained for routine examination, and treatment response and survival profiles as well as adverse events were evaluated. [Cell Death Dis] Full Article

T Cell Exhaustion Interrelates with Immune Cytolytic Activity to Shape Inflamed Tumor Microenvironment

Researchers defined a transcriptional signature for T cell exhaustion through analyzing differential gene expression between PD-1-high and PD-1-negative CD8⁺ T lymphocytes from primary non-small cell lung cancer, followed by positive correlation tests with PDCD1 in TCGA lung carcinomas. [Stem Cell Reports] Abstract

Human Leukocyte Antigen Alleles Associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

The authors performed high resolution human leukocyte antigen (HLA) -A, -B, -C, -DRB1, -DQB1 and -DPB1 genotyping by next generation sequencing in 426 adult, Norwegian myalgic encephalomyelitis/chronic fatigue syndrome patients, diagnosed according to the Canadian Consensus Criteria. HLA associations were assessed by comparing to 4511 healthy and ethnically matched controls. [Sci Rep] Full Article

A Case of Aberrant CD8 T Cell-Restricted IL-7 Signaling with a Janus Kinase 3 Defect-Associated Atypical Severe Combined Immunodeficiency

The authors describe a case involving a female infant who was referred to our institution on day nine of life following an abnormal newborn screen result for T−severe combined immunodeficiency. Immunological assessments revealed a T⁻B⁺NK⁺ phenotype and molecular analyses, including whole exome sequencing, identified compound heterozygous Janus Kinase 3 variants. [Immunol Res] Abstract

Identification of a Nerve-Associated, Lung-Resident Interstitial Macrophage Subset with Distinct Localization and Immunoregulatory Properties

Investigators report an interstitial subset of CD169⁺ lung-resident macrophages that were transcriptionally and developmentally distinct from alveolar macrophages. They were primarily localized around the airways and were found in close proximity to the sympathetic nerves in the bronchovascular bundle. [Sci Immunol] Full Article | Press Release

Therapeutic Targeting of Follicular T Cells with Chimeric Antigen Receptor-Expressing Natural Killer Cells

CAR-expressing human NK cells robustly and discriminately eliminated PD-1^high follicular human T cells in vitro and in a humanized mouse model of lupus-like disease while sparing B cells and other PD-1^low T cell subsets, including regulatory T cells. [Cell Rep Med] Full Article | Graphical Abstract

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mTOR Signaling at the Crossroads of Environmental Signals and T-Cell Fate Decisions

The authors review recent progress of the upstream signaling and downstream targets of mechanistic target of rapamycin (mTOR). They also provide an updated overview of the roles of mTOR in T-cell development, homeostasis, activation, and effector-cell fate decisions, as well as its important impacts on the suppressive activity of regulatory T cells. [Immunol Rev] Abstract

Life, Death, and Autophagy in Cancer: NF-κB Turns Up Everywhere

Although NF-κB is best known for its antiapoptotic role, other processes regulating the life/death balance, such as autophagy and necroptosis, seem to network with NF-κB. Investigators discuss how the reciprocal regulation of NF-κB, autophagy and programmed cell death affect cancer development and progression. [Cell Death Dis] Full Article

Visit our reviews page to see a complete list of reviews in the human immunology research field.

CytomX Therapeutics and Astellas Announce Strategic Collaboration to Develop Probody^® T-Cell Engaging Bispecific Therapies for Treatment of Cancer

CytomX Therapeutics, Inc. and Astellas Pharma Inc. announced they have entered into a strategic collaboration agreement focused on the discovery, research, development and commercialization of novel T-cell engaging bispecific antibodies targeting CD3 and tumor cell surface antigens for the treatment of cancer. [CytomX Therapeutics, Inc.] Press Release

Bristol Myers Squibb and bluebird bio Announce Submission of Biologics License Application (BLA) for Anti-BCMA CAR T Cell Therapy Idecabtagene Vicleucel (Ide-cel, bb2121) to FDA

Bristol Myers Squibb and bluebird bio, Inc. announced the submission of their BLA to the FDAfor idecabtagene vicleucel, the companies’ lead investigational B-cell maturation antigen (BCMA)-directed CAR-T cell immunotherapy, for the treatment of adult patients with multiple myeloma who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody. [Bristol Myers Squibb Company] Press Release

Cull, Release or Bring Them Home: Coronavirus Crisis Forces Hard Decisions for Labs With Animals

As universities scale back operations and scientists observe stay-at-home orders, many are struggling to protect their research and the animals that power it. [Nature News] Editorial

Tens of Thousands of Scientists Are Redeploying to Fight Coronavirus

As labs shut down around the world, researchers are finding creative ways to donate their time, supplies and expertise. [Nature News] Editorial

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NEW Associate Professor – Cancer Biology (University of Cincinnati)

Scientist – Cancer Immunology and Immunotherapy (Genentech, Inc.)

Co-Director – Anti-Cancer Immune Response (Rutgers Cancer Institute of New Jersey)

Research Fellow – Mucosal Immunology (University of Michigan)

Faculty Member – Neuro-Oncology (Wake Forest School of Medicine)

Postoctoral Scientist – Molecular and Cellular Immunology (Technical University of Munich)

Postdoctoral Researcher – Adoptive T-Cell Therapies (The University of Texas MD Anderson Cancer Center)

Postdoctoral Fellow – Cancer Immunology and Immunotherapy (Moffitt Cancer Center and Research Institute)

Postdoctoral Researchers – B Lymphocyte Regulation (NIH National Institute on Aging)

Research Fellow – Angiogenesis in Immune Regulation and Homing (Dana-Farber Cancer Institute)

Postdoctoral Fellow – Plasma Cell Development (Western Michigan University)

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