Human Immunology News Volume 5.46 | Nov 21 2017

TOP STORY

PD-1 Is a Haploinsufficient Suppressor of T Cell Lymphomagenesis

Researchers showed that the acute enforcement of oncogenic T cell receptor signaling in lymphocytes in a mouse model of human T cell lymphoma drives the strong expansion of these cells in vivo. However, this response was short-lived and robustly counteracted by cell-intrinsic mechanisms. [Nature] Abstract

(Ranked by impact factor of the journal)

Cyclin D–CDK4 Kinase Destabilizes PD-L1 via Cul3^SPOP to Control Cancer Immune Surveillance

The authors report that programmed cell death protein 1 ligand (PD-L1) protein abundance was regulated by cyclin D-CDK4 and the Cullin 3^SPOP E3 ligase via proteasome-mediated degradation. Inhibition of CDK4/6 in vivo elevated PD-L1 protein levels, largely by inhibiting cyclin D–CDK4-mediated phosphorylation of SPOP and thereby promoting SPOP degradation by APC/C^Cdh1. [Nature] Abstract

CD22-Targeted CAR T Cells Induce Remission in B-ALL that Is Naive or Resistant to CD19-Targeted CAR Immunotherapy

Scientists report results from a Phase I trial testing a new CD22-targeted CAR in 21 children and adults, including 17 who were previously treated with CD19-directed immunotherapy. [Nat Med] Abstract | Press Release | Editorial

Targeting the T Cell Receptor β-Chain Constant Region for Immunotherapy of T Cell Malignancies

Clinical application of immunotherapeutic approaches has been limited by a lack of target antigens that discriminate malignant from healthy T cells. Unlike B cell depletion, pan–T cell aplasia is prohibitively toxic. Investigators report a new targeting strategy based on the mutually exclusive expression of T cell receptor β-chain constant domains 1 and 2. [Nat Med] Abstract | Press Release

A Paradoxical Tumor-Suppressor Role for the Rac1 Exchange Factor Vav1 in T Cell Acute Lymphoblastic Leukemia

The authors report that the guanine exchange factor Vav1 unexpectedly possessed tumor-suppressor functions in immature T cells. This function entailed the noncatalytic nucleation of complexes between the ubiquitin ligase Cbl-b and the intracellular domain of Notch1 (ICN1) that favors ICN1 ubiquitinylation and degradation. [Cancer Cell] Full Article | Graphical Abstract

Integrated Genomic Analysis Identifies Deregulated JAK/STAT-MYC-Biosynthesis Axis in Aggressive NK-Cell Leukemia

Investigators performed the first comprehensive study of aggressive natural killer (NK)-cell leukemia by integrating whole genome, transcriptome and targeted sequencing, cytokine array as well as functional assays. Patient NK leukemia cells showed prominent activation of STAT3 phosphorylation, MYC expression and transcriptional activities in multiple metabolic pathways. [Cell Res] Full Article

Transcriptional Signature of Human Pro-Inflammatory T_H17 Cells Identifies Reduced IL10 Gene Expression in Multiple Sclerosis

Researchers showed that human peripheral blood IFN-γ⁺IL-17⁺ (T_H1/17) and IFN-γ⁻IL-17⁺ (T_H17) CD4⁺ T cells display distinct transcriptional profiles in high-throughput transcription analyses. Compared to T_H17 cells, T_H1/17 cells had gene signatures with marked similarity to mouse pathogenic T_H17 cells. [Nat Commun] Full Article

IL-2 Imprints Human Naive B Cell Fate towards Plasma Cell through ERK/ELK1-Mediated BACH2 Repression

To further understand mechanisms by which T cell inputs regulate B cell fate decision, scientists investigated the minimal IL-2 stimulation for triggering human plasma cell differentiation in vitro. They showed that the timed repression of BACH2 through IL-2-mediated ERK/ELK1 signaling pathway directs plasma cell lineage commitment. [Nat Commun] Full Article

Cancer Cells Induce Interleukin-22 Production from Memory CD4⁺ T Cells via Interleukin-1 to Promote Tumor Growth

Researchers hypothesized that IL-22 regulation would occur at the interface between cancer cells and immune cells. They found that IL-22 production in humans was dependent on activation of the NLRP3 inflammasome with the subsequent release of IL-1β from both myeloid and T cells. [Proc Natl Acad Sci USA] Abstract

Trigger-Happy Resident Memory CD4⁺ T Cells Inhabit the Human Lungs

The authors determined the transcriptional signature of CD4⁺ memory T cells (T_RM), identified by the expression of CD103, retrieved from human lung resection material. Various tissue homing molecules were specifically upregulated on CD4⁺ T_RM, whereas expression of tissue egress and lymph node homing molecules were low. [Mucosal Immunol] Abstract

MAFB Enhances Oncogenic Notch Signaling in T Cell Acute Lymphoblastic Leukemia

Scientists performed a gain-of-function screen to identify proteins that enhanced signaling by leukemia-associated Notch1 mutants. Decreasing MAFB abundance in mouse and human T cell acute lymphoblastic leukemia (T-ALL) cells reduced the expression of Notch1 target genes, including MYC and HES1, and sustained MAFB knockdown impaired T-ALL growth in a competitive setting. [Sci Signal] Full Article

Suppression of FIP200 and Autophagy by Tumor-Derived Lactate Promotes Naïve T Cell Apoptosis and Affects Tumor Immunity

Researchers report that naïve T cells were prone to undergo apoptosis due to a selective loss of FAK family–interacting protein of 200 kDa (FIP200) in ovarian cancer patients and tumor-bearing mice. This resulted in poor antitumor immunity via autophagy deficiency, mitochondria overactivation, and high reactive oxygen species production in T cells. [Sci Immunol] Abstract | Press Release

Subscribe to our sister publications: Immunology of Infectious Disease News & Immune Regulation News.

Microglia and Macrophages in Brain Homeostasis and Disease

The authors review the current knowledge of how and where brain macrophages are generated, with a focus on parenchymal microglia. They also discuss their normal functions during development and homeostasis, the disturbance of which may lead to various neurodegenerative and neuropsychiatric diseases. [Nat Rev Immunol] Abstract

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

Seres Therapeutics, MD Anderson Cancer Center, and the Parker Institute for Cancer Immunotherapy Announce a Collaboration to Support the Investigation of Microbiome Therapeutics for Immuno-Oncology

Seres Therapeutics, Inc., The University of Texas MD Anderson Cancer Center, and the Parker Institute for Cancer Immunotherapy announced a collaboration to evaluate the potential of Seres’ microbiome therapies to improve the outcomes of cancer patients treated with currently-available immunotherapy. [Seres Therapeutics, Inc.] Press Release

LLS Funds $46 Million in New Research to Find Cures

The Leukemia & Lymphoma Society^® (LLS) committed an additional $46 million to fund the most innovative science at leading medical institutions around the world, including Memorial Sloan Kettering Cancer Center in New York, Dana-Farber Cancer Institute in Boston, City of Hope in Duarte, California, and the Walter & Eliza Hall Institute of Medical Research in Australia. [The Leukemia & Lymphoma Society^®] Press Release

Celgene Corporation and bluebird bio Announce bb2121 Anti-BCMA CAR-T Cell Therapy Has Been Granted Breakthrough Therapy Designation from FDA and PRIME Eligibility from EMA for Relapsed and Refractory Multiple Myeloma

Celgene Corporation and bluebird bio, Inc. announced that bb2121, a CAR-T therapy targeting b-cell maturation antigen (BCMA) in previously treated patients with multiple myeloma, has been granted Breakthrough Therapy Designation by the FDA and PRIority MEdicines (PRIME) eligibility by the European Medicines Agency (EMA). [Celgene Corporation] Press Release

Seattle Children’s Opens First CAR T-Cell Immunotherapy Trial in the U.S. for Children and Young Adults with Leukemia that Targets CD22 and CD19 Proteins Simultaneously

Seattle Children’s has opened the first CAR T-cell immunotherapy trial in the U.S. for children and young adults with relapsed or refractory CD19- and CD22-positive acute lymphoblastic leukemia that will simultaneously attack two targets on cancer cells. [Seattle Children’s Hospital] Press Release

resTORbio Advances to Part 2 of a Phase IIb Clinical Study of RTB101 Immunotherapy

resTORbio, Inc. announced that an independent Data Monitoring Committee has unanimously recommended advancing an ongoing Phase IIb clinical study to Part 2 of the study. [resTORbio, Inc.] Press Release

Moderna Announces First-in-Human Dosing for Phase I Study (KEYNOTE-603) of mRNA-4157, a Personalized Cancer Vaccine, for the Treatment of Solid Tumors

Moderna Therapeutics announced that it has started dosing patients in a Phase I study of mRNA-4157, an mRNA-based personalized cancer vaccine. [Moderna Therapeutics] Press Release

Director of HHS Scientific Fraud Office Is out after Stormy 2-Year Tenure

The controversial director of the office that polices research fraud in U.S.-funded biomedical labs is temporarily moving to another agency. Kathy Partin has been removed after nearly two years as director of the U.S. Office of Research Integrity in Rockville, Maryland, according to Retraction Watch. [ScienceInsider] Editorial

European Medicines Agency Will Move to Amsterdam

The European Medicines Agency, charged with evaluating human and animal medicinal products for the European Union, will relocate to Amsterdam after it was selected in a draw of lots between it and Milan. [ScienceInsider] Editorial

Hungary Rewards Highly Cited Scientists with Bonus Grants

Some top researchers prosper in Hungary as country tries to improve its international standing in science. [Nature News] Editorial

Sudden Shift at a Public Health Journal Leaves Scientists Feeling Censored

For much of its 22-year existence, few outside the corner of science devoted to toxic chemicals paid much attention to the International Journal of Occupational and Environmental Health. But now, a feud has erupted over the small academic publication, as its editorial board — the scientists who advise the journal’s direction and handle article submissions — has accused the journal’s new owner of suppressing a paper and promoting “corporate interests over independent science in the public interest.” [Pro Publica Inc.] Editorial

NEW Keystone Symposia: Neuroinflammation: Causes, Concepts and Consequences
December 12, 2017
Online

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Positions – Cytokines in Immunity, Stem Cells and Tissue Repair (Weill Cornell Medicine)

Research Technologist – Immunotherapy (STEMCELL Technologies Inc.)

Scientist – Immunology (STEMCELL Technologies Inc.)

Postdoctoral Position – Immunology (Ghent University)

Postdoctoral Scientist – Molecular Genetics of Human T Cell Development (Ghent University)

Postdoctoral Fellow – Mucosal Immunology (University of Lorraine)

Postdoctoral Fellow – Mucosal Infections (University of Utah)

Postdoctoral Training Fellow – B Cell Immunology (The Francis Crick Institute)

Postdoctoral Positions – Rare Immune Disorders (Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases)

Tenured Track Faculty – Regenerative and Immune Engineering (Johns Hopkins University Biomedical Engineering)

Scientist – Immune Oncology (Dana-Farber Cancer Institute)

Postdoctoral Researcher – Immunology (University of Luxembourg)

Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.

Have we missed an important article or publication in Human Immunology News? Click here to submit!

Comments or suggestions? Submit your feedback here.