Immune Regulation News Volume 8.43 | Nov 25 2016

TOP STORY

Transcriptional Landscape of Human Tissue Lymphocytes Unveils Uniqueness of Tumor-Infiltrating T Regulatory Cells

Researchers found that tumor-infiltrating regulatory T (Treg) cells were highly suppressive, upregulated several immune-checkpoints, and expressed on the cell surfaces specific signature molecules such as interleukin-1 receptor 2, programmed death (PD)-1 Ligand1, PD-1 Ligand2, and CCR8 chemokine, which were not previously described on Treg cells. [Immunity] Full Article | Press Release

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Positive Regulation of Lyn Kinase by CD148 Is Required for B Cell Receptor Signaling in B1 but Not B2 B Cells

Investigators report that the Src-family kinase regulator CD148 has a unique and critical role in the initiation of B1 but not B2 cell antigen receptor signaling. CD148 loss-of-function mice were found to have defective B1 B-cell-mediated antibody responses against the T-cell-independent antigens NP-ficoll and Pneumovax 23 and had impaired selection of the B1 B cell receptor repertoire. [Immunity] Abstract | Graphical Abstract

TET Proteins Regulate the Lineage Specification and TCR-Mediated Expansion of iNKT Cells

Researchers found that simultaneous deletion of Tet2 and Tet3 in mouse CD4⁺CD8⁺ double-positive thymocytes resulted in dysregulated development and proliferation of invariant natural killer T cells (iNKT cells). [Nat Immunol] Abstract

Singular Role for T-BET⁺CXCR3⁺ Regulatory T Cells in Protection from Autoimmune Diabetes

Scientists characterized pancreas-infiltrating regulatory T (Treg) cells in the NOD mouse model of type 1 diabetes and uncovered a substantial enrichment of the Treg subpopulation expressing the chemokine receptor CXCR3. Accumulation of CXCR3⁺ Treg cells within pancreatic islets was dependent on the transcription factor T-BET, and genetic ablation of T-BET increased the onset and penetrance of disease, abrogating the sex bias normally seen in the NOD model. [Proc Natl Acad Sci USA] Abstract

Tailored Tumor Immunogenicity Reveals Regulation of CD4 and CD8 T Cell Responses against Cancer

The authors investigated the regulation of CD4 and CD8 T cell responses to different classes of tumor-specific antigens in liver cancer mouse models. [Cell Rep] Full Article | Graphical Abstract

Stress Kinase GCN2 Controls the Proliferative Fitness and Trafficking of Cytotoxic T Cells Independent of Environmental Amino Acid Sensing

Using GCN2-deficient strains crossed to T cell receptor transgenic backgrounds, researchers found GCN2 is essential for induction of stress target genes such as CHOP. However, GCN2-deficient CD8⁺ T cells fail to proliferate in limiting tryptophan, arginine, leucine, lysine, or asparagine, the opposite of what previous studies concluded. [Cell Rep] Full Article | Graphical Abstract

p38α Has an Important Role in Antigen Cross-Presentation by Dendritic Cells

The authors reported that the deletion of p38α resulted in an impaired cross-presentation ability of CD8⁺ conventional dendritic cells (cDCs) and a reduction in the direct presentation ability of CD8⁻ cDCs ex vivo. [Cell Mol Immunol] Abstract

Elevated Regulatory T Cells, Surface and Intracellular CTLA-4 Expression and Interleukin-17 in the Lung Cancer Microenvironment in Humans

Investigators detected the elements of immune response regulation in lung cancer in three compartments: by analysis of bronchoalveolar lavage fluid from the lung affected by cancer, healthy symmetrical lung and peripheral blood from the same patient. [Cancer Immunol Immunother] Full Article

Effect of Ex Vivo Expanded Recipient Regulatory T Cells on Hematopoietic Chimerism and Kidney Allograft Tolerance across MHC Barriers in Cynomolgus Macaques

CD4⁺CD25^high regulatory T cells (Treg) that were polyclonally expanded in culture were highly suppressive in vitro and maintained high expression of FoxP3. Eight monkeys underwent nonmyeloablative conditioning and MHC-mismatched BMT with or without Treg infusion. [Transplantation] Abstract

Gemcitabine Treatment Enhanced the Anti-Tumor Effect of Cytokine Induced Killer Cells by Depletion of CD4⁺CD25^bri Regulatory T Cells

An In vivo experiment showed that low dose of gemcitabine treated cytokine induced killer cells significantly suppressed tumor growth and prolonged their lifespan in tumor-bearing nude mice, with the proportion of CD4⁺CD25^bri regulatory T cells reduced. [Immunol Lett] Abstract

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Foxp3, Regulatory T Cell, and Autoimmune Diseases

Researchers summarized three main prospects: the regulatory mechanism of forkhead box P3 (Foxp3), the influence on Foxp3 and regulatory T cells (Tregs) in autoimmune diseases, then finally, how Tregs can be used to treat autoimmune diseases. [Inflammation] Abstract

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Juno Therapeutics Places JCAR015 Phase II ROCKET Trial on Clinical Hold

Juno Therapeutics, Inc. announced that it has voluntarily placed on hold the Phase II clinical trial of JCAR015 in adult patients with relapsed or refractory B cell acute lymphoblastic leukemia, known as the “ROCKET” trial. [Juno Therapeutics, Inc.] Press Release

Darzalex^® (Daratumumab) Approved by U.S. FDA in Combination with Two Standard of Care Regimens for the Treatment of Patients with Multiple Myeloma who Have Received at Least One Prior Therapy

Janssen Biotech, Inc. announced the U.S. Food and Drug Administration (FDA) has approved DARZALEX^® in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy. [Janssen Biotech, Inc.] Press Release

UK Scientists Excited by Surprise £2-Billion Government Windfall

UK Chancellor of the Exchequer Philip Hammond has announced a large boost in funding for research and development (R&D). The government is expecting to spend an extra £4.7 billion on R&D between now and 2020–21, and the final year’s £2-billion boost will represent a rise of around 20% in total government R&D spending. [Nature News] Editorial

NgAgo Gene-Editing Controversy Escalates in Peer-Reviewed Papers

A heated dispute over gene-editing that began online is now playing out in the scientific literature. Six months ago, Chinese researchers reported that an enzyme called NgAgo could be used to edit mammalian genes – and that it might be more accurate and more versatile than the popular CRISPR-Cas9 gene-editing technique. [Nature News] Editorial

Immigrant and Minority Scientists Shaken by Trump Win

Scientists are reconsidering whether to work or study in the United States. Worries include job prospects, discrimination—and safety. [Nature News] Editorial

Peer-Review ‘Heroes’ Do Lion’s Share of the Work

In 2015, the number of scientists in the life sciences far exceeded the demand on them for peer review, according to Michail Kovanis, a computational physicist at the French National Institute of Health and Medical Research in Paris, and his colleagues. Yet their study also suggests – based on data obtained from a rapidly-growing website of peer-review activity – that 20% of the scientists undertook between 69% and 94% of reviews last year, lending credence to some researchers’ complaints that they are overburdened. [Nature News] Editorial

NEW Keystone Symposium: Pattern Recognition Signaling: From Innate Immunity to Inflammatory Disease
March 19-23, 2017
Banff, Canada

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