Immune Regulation News Volume 10.43 | Nov 9 2018

TOP STORY

The Metabolite BH4 Controls T Cell Proliferation in Autoimmunity and Cancer

Investigators found that genetic inactivation of GTP cyclohydrolase 1 and inhibition of sepiapterin reductase severely impaired the proliferation of mature mouse and human T cells. [Nature] Abstract | Press Release

(Ranked by impact factor of the journal)

Perivascular Dendritic Cells Elicit Anaphylaxis by Relaying Allergens to Mast Cells via Microvesicles

Scientists describe the existence of a CD301b⁺ perivascular dendritic cell subset that continuously samples blood and relays antigens to neighboring mast cells, which vigorously degranulate and trigger anaphylaxis. [Science] Abstract | Press Release

Tumor Immunoevasion via Acidosis-Dependent Induction of Regulatory Tumor-Associated Macrophages

Researchers explored a molecular mechanism of metabolic communication deployed by highly glycolytic tumors for immunoevasion. In contrast to colon adenocarcinomas, melanomas showed comparatively high glycolytic activity, which resulted in high acidification of the tumor microenvironment. [Nat Immunol] Abstract

Interleukin-17 Drives Interstitial Entrapment of Tissue Lipoproteins in Experimental Psoriasis

Scientists found that psoriasis-affected skin lesions program interleukin-17-producing T cells in draining lymph nodes to home to distal skin and later to arteries. [Cell Metab] Abstract | Press Release | Graphical Abstract

Dynamic Control of Proinflammatory Cytokines Il-1β and TNF-α by Macrophages in Zebrafish Spinal Cord Regeneration

Researchers showed that inhibiting inflammation reduced and promoting it accelerated axonal regeneration in spinal-lesioned zebrafish larvae. Mutant analyses showed that peripheral macrophages, but not neutrophils or microglia, were necessary for repair. [Nat Commun] Full Article | Press Release

B Cell Receptor Crosslinking Augments Germinal Center B Cell Selection when T Cell Help Is Limiting

By adapting an experimental approach that enables independent delivery of B cell receptor-crosslinking antigen or T cell help to germinal center (GC) B cells in vivo, the authors showed that T cell help was sufficient to induce GC B cell expansion and plasmablast formation. [Cell Rep] Full Article | Graphical Abstract

Genetic Models Reveal cis and trans Immune-Regulatory Activities for lincRNA-Cox2

Investigators characterized multiple models of long intergenic non-coding RNA (lincRNA)-Cox2-deficient mice. LincRNA-Cox2-deficient macrophages and murine tissues had altered expression of inflammatory genes. [Cell Rep] Full Article | Press Release | Graphical Abstract

VISTA Expressed in Tumor Cells Regulates T Cell Function

Scientists investigated V-domain Ig suppressor of T cell activation (VISTA) expression and function in tumor cells, and evaluated its mechanism and activity. [Br J Cancer] Full Article

Integrated B Cell, Toll-Like, and BAFF Receptor Signals Promote Autoantibody Production by Transitional B Cells

The authors interrogated the B cell signals required for transitional B cell transmembrane activator and CAML interactor (TACI) expression and Ab production. Surprisingly, despite established roles for dual BCR and TLR signals in autoantibody (autoAb) production in systemic lupus erythematosus, signals downstream of these receptors exerted distinct impacts on transitional B cell TACI expression and autoAb titers. [J Immunol] Abstract

Increased Mitochondrial Biogenesis and Reactive Oxygen Species Production Accompany Prolonged CD4⁺ T Cell Activation

Investigators showed that for four days following activation, mouse CD4⁺ T cells sustained their commitment to glycolysis facilitated by increased glucose uptake through increased expression of GLUT transporters. [J Immunol] Abstract

Depletion of Regulatory T Cells in Ongoing Paracoccidioidomycosis Rescues Protective Th1/Th17 Immunity and Prevents Fatal Disease Outcome

Treg cell depletion was achieved by treatment of transgenic C57BL/6^DTR/eGFP mice with diphtheria toxin after three weeks of intratracheal infection with 1×10⁶ Paracoccidioides brasiliensis yeasts. [Sci Rep] Full Article

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Hypoxia-Inducible Factor-1α Regulation of Myeloid Cells

Researchers summarize recent advances that have elucidated the mechanism by which myeloid cells regulate hypoxia-inducible factor (HIF)-1α activity and, in turn, how HIF-1α shapes myeloid cell function. [J Mol Med] Abstract

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OncoMed Announces Early Clinical Data for Anti-TIGIT Antibody

OncoMed Pharmaceuticals, Inc. announced initial results from the Phase Ia dose escalation portion of a Phase Ia/b trial of etigilimab, the company’s anti-TIGIT antibody. [Press release from OncoMed Pharmaceuticals, Inc. discussing research presented at the 2018 Society for Immunotherapy of Cancer (SITC) Meeting, Washington] Press Release

NantKwest Announces Promising First in Human Clinical Results of 300 Doses Of CD16 Targeted, Off-the-Shelf Cryopreserved Natural Killer Cells (haNK) in a Novel Cancer Memory Vaccine Immunotherapy

From August 2017 to October 2018, safety and efficacy clinical trials were completed using a novel first-in-human combination immunotherapy cancer vaccine. [Press release from NantKwest discussing research presented at the 2018 Society for Immunotherapy of Cancer (SITC) Meeting, Washington] Press Release

Early Phase I Data from Merck’s Oncology Pipeline for Investigational Anti-LAG-3 Therapy (MK-4280) and Anti-TIGIT Therapy (MK-7684) to Be Presented

Merck announced the first presentations of preliminary safety and efficacy data from Phase I/II dose finding studies for the company’s investigational anti-LAG-3 therapy and anti-TIGIT therapy in patients with advanced solid tumors. [Press release from Merck & Co., Inc. discussing research presented at the 2018 Society for Immunotherapy of Cancer (SITC) Meeting, Washington] Press Release

Synlogic Presents Preclinical Data from First Synthetic Biotic™ Clinical Candidate in Immuno-Oncology

Synlogic, Inc. announced the presentation of preclinical data from its first immuno-oncology program. [Press release from Synlogic, Inc. discussing research presented at the 2018 Society for Immunotherapy of Cancer (SITC) Meeting, Washington] Press Release

X4 Pharmaceuticals Presents Clinical Data Demonstrating Single Agent X4P-001-IO Enhances Tumor Immunity through CXCR4 Antagonism

X4 Pharmaceuticals highlighted data from a poster presentation of a clinical study with X4P-001-IO, an investigational CXCR4 allosteric antagonist. [Press release from X4 Pharmaceuticals discussing research presented at the 2018 Society for Immunotherapy of Cancer (SITC) Meeting, Washington] Press Release

Lilly and NextCure Announce Collaboration to Discover and Develop Novel Immuno-Oncology Medicines

Eli Lilly and Company and NextCure, Inc. announced a multi-year collaboration focused on the discovery and development of immuno-oncology therapies. The collaboration seeks to discover novel cancer targets utilizing NextCure’s proprietary FIND-IO™ platform. [Eli Lilly and Company] Press Release

Brooklyn ImmunoTherapeutics Acquires IRX Therapeutics

IRX Therapeutics, Inc. announced that the company’s assets have been acquired by the newly formed Brooklyn ImmunoTherapeutics LLC. This name reflects the company’s focus on advancing the science of cytokine-based immunotherapy for the treatment of a range of cancers. [Brooklyn ImmunoTherapeutics] Press Release

Visterra Initiates Phase I Clinical Study of VIS649

Visterra, Inc. announced the initiation of a Phase I clinical study with VIS649 in healthy volunteers. [Visterra, Inc.] Press Release

Mirati Therapeutics Announces First Patient Dosed in Phase Ib Clinical Trial of Sitravatinib in Combination with Anti-PD1 Antibody Tislelizumab in Patients with Advanced Solid Tumors

Mirati Therapeutics, Inc. announced dosing of the first patient under its collaboration agreement with BeiGene, Ltd. in a Phase Ib clinical trial to assess the safety and tolerability, pharmacokinetics and preliminary anti-tumor activity of Mirati’s sitravatinib in combination with BeiGene’s investigational anti-PD1 antibody, tislelizumab, in patients with advanced solid tumors. [Mirati Therapeutics, Inc.] Press Release

Sanger Whistle-Blowers Dispute Findings That Cleared Management of Bullying

Current and former employees say investigation at the Wellcome Sanger Institute was flawed; the genomics powerhouse stands by the findings. [Nature News] Editorial

Scientists Struggle with Confusing Journal Guidelines

Globally, more than two-thirds of researchers find it difficult to prepare manuscripts and to respond to peer-review comments, finds a survey of nearly 7,000 researchers from over 100 countries. [Nature News] Editorial

Open-Access Plan Draws Online Protest

Hundreds of scientists are pushing back against Plan S, a plan to crack down on scholarly journals’ paywalls, launched 2 months ago by 11 national research funders in Europe. In an open letter published on 5 November, about 800 signatories say they support open access—making papers available free to all readers online—but condemn Plan S as “too risky for science.” [ScienceInsider] Editorial

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