Immune Regulation News Volume 11.15 | May 3 2019

TOP STORY

Researchers Find New Target to Improve Response to Cancer Immunotherapy

Researchers looked at a little-understood type of cell death called ferroptosis. They found ferroptosis occurs in tumor cells and plays a role in cancer immunity, suggesting the potential of targeting this pathway to improve immunotherapy treatments. [Press release from the University of Michigan Rogel Cancer Center discussing online prepublication in Nature] Press Release | Abstract

(Ranked by impact factor of the journal)

The Chemoattractant Receptor Ebi2 Drives Intranodal Naive CD4⁺ T Cell Peripheralization to Promote Effective Adaptive Immunity

Scientists report that the peripheral localization of lymph node cDC2 dendritic cells specialized for MHC-II antigen presentation was matched by a similarly biased paracortical distribution of CD4⁺ T cells directed by the chemoattractant receptor Ebi2. [Immunity] Abstract | Graphical Abstract

Bone Marrow Dendritic Cells Regulate Hematopoietic Stem/Progenitor Cell Trafficking

The authors showed that murine bone marrow dendritic cells (DCs) are perivascular and have a type 2 conventional DC (cDC2) immunophenotype. RNA expression analysis of sorted bone marrow DCs showed that expression of many chemokines and chemokine receptors was distinct from that observed in splenic cDC2s, suggesting that bone marrow DCs may represent a unique DC population. [J Clin Invest] Abstract | Full Article | Graphical Abstract

Loss of TET2 and TET3 in Regulatory T Cells Unleashes Effector Function

Investigators examined the role of TET proteins in Treg cells. Tet2/3^fl/flFoxp3^Cre mice lacking Tet2 and Tet3 in Treg cells developed inflammatory disease, and Treg cells from these mice showed altered expression of Treg signature genes and upregulation of genes involved in cell cycle, DNA damage and cancer. [Nat Commun] Full Article

Contact-Dependent Killing by Cytotoxic T Lymphocytes Is Insufficient for EL4 Tumor Regression In Vivo

Researchers developed an agent-based model and an ordinary differential equation model of tumor regression after adoptive transfer of a population of cytotoxic T lymphocyte (CTLs). Models were parameterized based on in vivo measurements of CTL infiltration and killing rates applied to EL4/EG7 tumors and OTI T cells. [Cancer Res] Abstract

Distinct Requirements of CHD4 during B Cell Development and Antibody Response

Scientists found that CHD4 was essential for early B cell development but was dispensable for the homeostatic maintenance of mature, naive B cells. [Cell Rep] Full Article | Graphical Abstract

Aryl Hydrocarbon Receptor Interacting Protein Maintains Germinal Center B Cells through Suppression of BCL6 Degradation

Deletion of aryl hydrocarbon receptor interacting protein in B cells decreased B cell lymphoma-6 (BCL6) expression, reducing germinal center B cells and diminishing adaptive immune responses. [Cell Rep] Full Article | Graphical Abstract

Reducing IRF5 Expression Attenuates Colitis in Mice, but Impairs the Clearance of Intestinal Pathogens

Investigators found that deleting IRF5 in mice led to reduced intestinal inflammation in the T cell transfer colitis model, with reduced Th1 and Th17, and increased Th2 cytokines. However, with orally-administered invasive S. typhimurium, IRF5^−/− mice demonstrated an increased bacterial burden in the context of reduced Th1 and Th17 cytokines. [Mucosal Immunol] Abstract

Combined Antitumor Effects of Sorafenib and GPC3-CAR T Cells in Immunocompetent and Immunodeficient Mouse Models of Hepatocellular Carcinoma

Researchers analyzed the combined effect of GPC3 CAR T cells and sorafenib both in immunocompetent and immunodeficient mouse models of hepatocellular carcinoma. [Mol Ther] Abstract

MRP14 Enhances the Ability of Macrophage to Recruit T Cells and Promotes Obesity-Induced Insulin Resistance

Scientists investigated the role of myeloid-related protein-14 (MRP14) in macrophage-mediated adipose tissue inflammation and obesity-induced insulin resistance. [Int J Obes] Abstract

TET Enzymes Augment Activation-Induced Deaminase (AID) Expression via 5-Hydroxymethylcytosine Modifications at the Aicda Superenhancer

Investigators report a close correspondence between 5-hydroxymethylcytosine-marked regions, chromatin accessibility and enhancer activity in B cells, and a strong enrichment for consensus binding motifs for basic region-leucine zipper transcription factors at TET-responsive genomic regions. [Sci Immunol] Full Article

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New Insights into the Immune Functions of Complement

The authors consider fundamental mechanisms and novel concepts at the interface of complement biology and immunity and discuss how these affect the maintenance of homeostasis and the development of human pathology. [Nat Rev Immunol] Abstract

Visit our reviews page to see a complete list of reviews in the immune regulation research field.

Mallinckrodt to Present Open-Label Results from Phase IV Acthar^® Gel (Repository Corticotropin Injection) Clinical Trial in Patients with Rheumatoid Arthritis

Mallinckrodt plc has completed the controlled, double-blind, randomized second phase of the ongoing Phase IV, multicenter study assessing the efficacy and safety of Acthar^® Gel in patients with persistently active rheumatoid arthritis who were previously treated with disease-modifying anti-rheumatic drugs and corticosteroids. [Press release from Mallinckrodt plc discussing research to be presented at the 2019 Annual European Congress of Rheumatology (EULAR), Madrid] Press Release

Multiple Myeloma Research Foundation (MMRF) Venture Philanthropy Fund Invests in NexImmune to Advance Novel Immunotherapy Candidate into Clinical Trials

NexImmune and the MMRF have entered into a partnership to advance a promising new therapy into clinical trials for multiple myeloma patients. [Multiple Myeloma Research Foundation] Press Release

Fondren Foundation Commits $15 Million to Houston Methodist to Pioneer Treatments

The Fondren Foundation has made a $15 million commitment to Houston Methodist to support the Food and Health Alliance, the Immunology Center and to create the Fondren Inflammation Collaborative, a new multidisciplinary program that will provide hope for people with complex allergy, immunologic, autoimmune and GI conditions. [The Fondren Foundation (American Association for the Advancement of Science)] Press Release

PCI Biotech: Successful Clinical Translation of the fimaVacc Technology

PCI Biotech announced that the final immune response results from the fimaVacc Phase I study in healthy volunteers indicate a clear enhancement of both CD8 and CD4 T-cell responses and an improved CD8 T-cell functionality after vaccination at tolerable dose levels. [PCI Biotech (GlobeNewswire, Inc.)] Press Release

German Research Promised a Decade of Budget Increases

German research organizations cheered a decision announced by state and federal ministers to increase research budgets by 3% a year for the next decade—a total boost of €17 billion over that time. [ScienceInsider] Editorial

Senator’s Queries Prompt NIH and NSF to Clarify How They Monitor Foreign Research Ties

Responding to the rising concern within Congress that foreign governments are taking advantage of the open US research enterprise, the National Institutes of Health (NIH) and the National Science Foundation (NSF) have recently tweaked their grantmaking process to better monitor the foreign ties of the researchers they fund. [ScienceInsider] Editorial

NEW ISCT North America 2019 Regional Meeting
September 13-15, 2019
Madison, Wisconsin, United States

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

NEW Postdoctoral Fellow – Transplantation Immunology (Medical College of Wisconsin)

NEW Professorship- Translational Immune Oncology (Uniklinik Köln)

Postdoctoral Position – Immunology of Enteric Infections (University of Utah)

Senior Staff Scientist – Functional Genomics (Wellcome Sanger Institute)

Director of Research – Division of Translational Medicine & Human Genetics (University of Pennsylvania)

Postdoctoral Fellow – Immuno-Oncology (Georgetown Lombardi Comprehensive Cancer Center)

Faculty Position – Immunology (Fox Chase Cancer Center)

Associate Scientist – Immuno-Oncology (HMH Center for Discovery & Innovation)

Postdoctoral Fellow – Cancer Checkpoint Immunotherapy (City of Hope)

Assistant/Associate or Professor – Cancer Immunotherapy/Tumor Immunology (University of California, Irvine)

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