Immune Regulation News Volume 8.42 | Nov 18 2016

TOP STORY

Overcoming Resistance to Checkpoint Blockade Therapy by Targeting PI3Kγ in Myeloid Cells

Scientists employed a pre-clinical mouse model system and showed that resistance to immune checkpoint blocking (ICB) is directly mediated by the suppressive activity of infiltrating myeloid cells in various tumors. Furthermore, selective pharmacologic targeting of the gamma isoform of phosphoinositide 3-kinase (PI3Kγ), highly expressed in myeloid cells, restores sensitivity to ICB. [Nature] Abstract | Press Release

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Aire Inhibits the Generation of a Perinatal Population of Interleukin-17A-Producing γδ T Cells to Promote Immunologic Tolerance

Researchers found that Aire-deficient mice had expanded thymic and peripheral populations of perinatally generated IL-17A⁺Vγ6⁺Vδ1⁺ T cells, considered to be “early responders” to tissue stress and drivers of inflammatory reactions. [Immunity] Abstract | Graphical Abstract

Gradients of the Signaling Lipid S1P in Lymph Nodes Position Natural Killer Cells and Regulate their Interferon-γ Response

Natural killer (NK) cells are located at the periphery of the lymph node, predominantly in the medulla, and scientists found that expression of SPNS2, expression of the sphingosine 1-phosphate (S1P) receptor S1PR5 on NK cells, and expression of the chemokine receptor CXCR4 were all required for NK cell localization during homeostasis and rapid production of interferon-γ by NK cells after challenge. [Nat Immunol] Abstract

A Myc-Dependent Division Timer Complements a Cell-Death Timer to Regulate T Cell and B Cell Responses

T lymphocytes and B lymphocytes integrate activating signals to control the size of their proliferative response. Investigators report that such control was achieved by timed changes in the production rate of cell-cycle-regulating proto-oncoprotein Myc, with division cessation occurring when Myc levels fell below a critical threshold. [Nat Immunol] Abstract

Glutaminolysis and Fumarate Accumulation Integrate Immunometabolic and Epigenetic Programs in Trained Immunity

Through network-level integration of transcriptomics and metabolomics data, scientists identified glycolysis, glutaminolysis, and the cholesterol synthesis pathway as indispensable for the induction of trained immunity by β-glucan in monocytes. [Cell Metab] Full Article | Graphical Abstract

Linear Ubiquitin Chain Assembly Complex Coordinates Late Thymic T-Cell Differentiation and Regulatory T-Cell Homeostasis

Researchers showed that the linear ubiquitin chain assembly complex components HOIP, HOIL-1 and SHARPIN have essential roles in late thymocyte differentiation, FOXP3⁺ regulatory T (Treg)-cell development and Treg cell homeostasis. [Nat Commun] Full Article | Press Release

USP21 Prevents the Generation of T-Helper-1-Like Treg Cells

The authors report that the E3 deubiquitinase USP21 prevents the depletion of FOXP3 at the protein level and restricts the generation of T-helper-1-like regulatory T (Treg) cells. Mice depleted of Usp21 specifically in Treg cells display immune disorders characterized by spontaneous T-cell activation and excessive T-helper type 1 (Th1) skewing of Treg cells into Th1-like Treg cells. [Nat Commun] Full Article

Heparanase Is Required for Activation and Function of Macrophages

Researchers used a genetic approach and examined the behavior and function of macrophages isolated from wild-type and heparanase-knockout (Hpa-KO) mice. Hpa-KO macrophages express lower levels of cytokines and exhibit lower motility and phagocytic capacities. [Proc Natl Acad Sci USA] Abstract

Regulatory B Cells Induce Formation of IL-10 Expressing T Cells in Mice with Autoimmune Neuroinflammation

The authors showed that regulatory B cells can induce formation of conventional FoxP3⁺ regulatory T cells, as well as a more recently described CD49b⁺CD223⁺ regulatory T cell subset, known as type 1 regulatory T cells. [J Neurosci] Abstract

Doxycycline, Metronidazole and Isotretinoin: Do They Modify MicroRNA/mRNA Expression Profiles and Function in Murine T-Cells?

Isotretinoin induced IL-10 signaling in Tregs and naive T-cells directly after treatment and reduced effector T-cell proliferation alone and in co-culture with Tregs. [Sci Rep] Full Article

Tuftsin Prevents the Negative Immunoregulation of Neuropilin-1^highCD4⁺CD25⁺Regulatory T Cells and Improves Survival Rate in Septic Mice

Tuftsin prevented the negative immunoregulation of neuropilin (Nrp)-1^highCD4⁺CD25⁺regulatory T cells (Tregs), including weakening the expression of forkhead/winged helix transcription factor- 3/cytotoxic T lymphocyte associated antigen-4, inhibiting the secretion of transforming growth factor-β, and weakening the immunosuppressive function of Nrp-1^highCD4⁺CD25⁺Tregs to conventional CD4⁺CD25^–T cells. [Oncotarget] Full Article

Imbalance of Th17/Treg in Different Subtypes of Autoimmune Thyroid Diseases

Scientists aimed to clarify the imbalance of Th17/Treg in different subtypes of autoimmune thyroid diseases including Graves’ disease, Hashimoto’s thyroiditis and Graves’ ophthalmopathy. [Cell Physiol Biochem] Abstract | Full Article

Granulocyte Colony-Stimulating Factor Treatment Ameliorates Lupus Nephritis through the Expansion of Regulatory T Cells

Granulocyte colony-stimulating factor (G-CSF) treatment induced expansion of CD4⁺CD25⁺Foxp3⁺ regulatory T cells, with decreased renal infiltration of T cells, B cells, inflammatory granulocytes and monocytes in both kidneys and spleen. G-CSF treatment also decreased expression levels of MCP-1, IL-6, IL-2, and IL-10 in renal tissues as well as serum levels of MCP-1, IL-6, TNF-α, IL-10, and IL-17. [BMC Nephrol] Full Article

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Impact of Inhibitor of Apoptosis Proteins on Immune Modulation and Inflammation

The authors focus on modulation of the innate and adaptive immune systems, macrophage plasticity and inflammatory responses by IAP family members. They also explore the rationale to target IAPs pharmacologically for the treatment of a number of inflammatory diseases and cancer. [Immunol Cell Biol] Full Article

Essential Role of Interferon Regulatory Factor 4 (IRF4) in Immune Cell Development

The roles of IRF4 in the immune response are briefly summarized and discussed, with particular focus on its essential and distinct functions in immune cell development. [Arch Pharm Res] Abstract

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NANOBIOTIX Presents NBTXR3 Preclinical Data Demonstrating Its Potential Usage as In Situ Vaccine for Cancer

NANOBIOTIX announced preclinical data demonstrating that its leading radioenhancer nanoparticle, NBTXR3, actively stimulates the host immune system to attack tumor cells. [Press release from NANOBIOTIX discussing research presented at the 31^st Annual Meeting of the Society for Immunotherapy of Cancer (SITC), National Harbor] Press Release

Roche Launches imCORE, a Global Network of Cancer Immunotherapy Centers of Excellence

Roche launched the global cancer immunotherapy Centers of Research Excellence (imCORE™) Network. This network brings together many of the world’s leading scientific and clinical experts in cancer immunotherapy to collaborate in investigating the most promising new treatment approaches. [F. Hoffmann-La Roche Ltd] Press Release

Pfizer to Collaborate with National Cancer Institute to Study Three Immunotherapy Agents Targeting Multiple Cancers

Pfizer Inc. announced that it has entered into a Cooperative Research and Development Agreement with the National Cancer Institute, part of the National Institutes of Health. [Pfizer Inc.] Press Release

Selexis SA and OSE Immunotherapeutics Collaborate to Advance Development of Immunotherapies for Cancer and Autoimmune Diseases

Selexis SA and OSE Immunotherapeutics SA announced the signing of two service agreements that provide OSE Immunotherapeutics with access to high performance research cell banks from the Selexis SUREtechnology Platform™. [Selexis SA] Press Release

Neon Therapeutics Announces First Patient Enrolled in Inaugural Clinical Trial for Personalized Cancer Vaccine NEO-PV-01

Neon Therapeutics announced that it has enrolled the first patient at the University of Texas MD Anderson Cancer Center in its first company-sponsored clinical trial evaluating its lead program, NEO-PV-01. [Neon Therapeutics] Press Release

MabVax Therapeutics Reports Interim Safety and Imaging Results from Phase I Clinical Trials in HuMab-5B1 Antibody Development Programs

MabVax Therapeutics Holdings, Inc. reported on progress from its two HuMab-5B1 antibody Phase I programs evaluating the use of MVT-5873 as a therapeutic antibody and MVT-2163 as an immuno-PET imaging agent in patients with locally advanced and metastatic pancreatic cancer or other CA19-9 positive malignancies. [MabVax Therapeutics Holdings, Inc.] Press Release

Brazil’s Scientists Battle to Escape 20-Year Funding Freeze

Brazil’s science budget has shrunk by more than 40% in the past three years. But researchers are now trying to escape an even worse crisis: federal science spending could be frozen at its current low level for the next two decades, under a constitutional amendment to cap public spending to only inflation-level rises. [Nature News] Editorial

UK Politicians Demand Brexit Guarantee for EU Scientists

Ever since June’s Brexit referendum, scientists have fretted about the uncertainty caused for non-British EU nationals, who have been left unsure what their employment rights may be in a few years’ time. There are around 31,000 such researchers in the United Kingdom, according to a Royal Society estimate, and they make up about 15% of UK universities’ academic staff. [Nature News] Editorial

Argentina President’s First Budget Angers Scientists

Researchers in Argentina are incensed about budget cuts that look set to hit the nation’s science ministry especially hard next year—even though President Mauricio Macri pledged to boost science spending when he took office. [Nature News] Editorial

Biomedical Research Leaders Urge Trump Administration to Quickly Appoint an NIH Director

A science star–studded group that including two former directors of the National Institutes of Health (NIH) in Bethesda, Maryland, released a set of recommendations aimed at making NIH run better and offered advice on choosing an NIH director—ideally within Trump’s first 100 days in office. [Science Insider] Editorial

In Bold New Step, Dutch Science Academy Holds Women-Only Elections

In order to reduce its perpetual gender imbalance—87% of its 556 members are men—the Royal Netherlands Academy of Arts and Sciences seeks to recruit ten new members in 2017 and six more in 2018, all with two X chromosomes. [ScienceInsider] Editorial

How Self-Appointed Guardians of “Sound Science” Tip the Scales toward Industry

At a time when public mistrust of science runs high, and non-experts are hard-pressed to separate fact from industry-sponsored spin, Sense About Science, a charity based in London with an affiliate in New York, presents itself as a trustworthy arbiter. The organization purports to help the misinformed public sift through alarmist claims about public health and the environment by directing journalists, policymakers, and others to vetted sources who can explain the evidence behind debates about controversial products like e-cigarettes and flame retardants. [The Intercept] Editorial

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