Immune Regulation News Volume 10.01 | Jan 12 2018

TOP STORY

Mechanism for Resistance to Immunotherapy Treatment Discovered

Dana-Farber researchers say discovery may help identify kidney cancer and melanoma patients that will benefit from checkpoint inhibitor treatment. [Press release from Dana-Farber Cancer Institute discussing online prepublication in Science] Press Release | Abstract

(Ranked by impact factor of the journal)

The Epigenetic Control of Stemness in CD8⁺ T Cell Fate Commitment

The authors explored the role of gene silencing by the histone methyltransferase Suv39h1. In murine CD8⁺ T cells activated after Listeria monocytogenes infection, Suv39h1-dependent trimethylation of histone H3 lysine 9 controlled the expression of a set of stem cell-related memory genes. [Science] Abstract

LXR/ApoE Activation Restricts Innate Immune Suppression in Cancer

Through genetic and pharmacological approaches, scientists uncovered a pathway governing myeloid-derived suppressor cell (MDSC) abundance in multiple cancer types. Therapeutic liver-X nuclear receptor (LXR) agonism reduced MDSC abundance in murine models and in patients treated in a first-in-human dose escalation Phase I trial. [Cell] Abstract | Press Release | Graphical Abstract

Modulation of Myelopoiesis Progenitors Is an Integral Component of Trained Immunity

Researchers hypothesized that trained immunity acts via modulation of hematopoietic stem and progenitor cells. The trained-immunity-related increase in myelopoiesis resulted in a beneficial response to secondary LPS challenge and protection from chemotherapy-induced myelosuppression in mice. [Cell] Full Article | Press Release | Graphical Abstract

Diverse Genetic-Driven Immune Landscapes Dictate Tumor Progression through Distinct Mechanisms

Scientists characterized the immune-cell composition of prostate cancers driven by the loss of the critical tumor suppressor gene Pten, either alone or in combination with the loss of Trp53, Zbtb7a or Pml. [Nat Med] Abstract

TIM-3 Regulates CD103⁺ Dendritic Cell Function and Response to Chemotherapy in Breast Cancer

Investigators evaluated the expression of immune regulators by CD103⁺ dendritic cells in a murine model of breast cancer and identified expression of TIM-3 as a target for therapy. Anti-TIM-3 antibody improved response to paclitaxel chemotherapy in models of triple-negative and luminal B disease, with no evidence of toxicity. [Cancer Cell] Abstract | Graphical Abstract

Intravital Mucosal Imaging of CD8⁺ Resident Memory T Cells Shows Tissue-Autonomous Recall Responses that Amplify Secondary Memory

The authors used two-photon intravital microscopy to visualize the responses of CD8⁺ resident memory T cells (T_RM cells) within the reproductive tracts of live female mice. T_RM cells could autonomously regulate the expansion of local immunosurveillance independently of central memory or proliferation in lymphoid tissue. [Nat Immunol] Abstract

Let-7 Suppresses B Cell Activation through Restricting the Availability of Necessary Nutrients

Investigators employed several engineered mouse models, including B cell-specific overexpression of Lin28a or the let-7a-1/let-7d/let-7f-1 cluster (let-7adf) and knockout of individual let-7 clusters, to show that let-7adf specifically inhibits T cell-independent antigen-induced immunoglobulin M antibody production. [Cell Metab] Abstract | Graphical Abstract

A miRNA181a/NFAT5 Axis Links Impaired T Cell Tolerance Induction with Autoimmune Type 1 Diabetes

The authors showed that enhancing miRNA181a activity increases NFAT5 expression while inhibiting FOXP3⁺ T_reg induction in vitro. Accordingly, T_reg induction was improved using T cells from NFAT5 knockout (NFAT5ko) animals, whereas altering miRNA181a activity did not affect T_reg induction in NFAT5ko T cells. [Sci Transl Med] Abstract | Press Release

Targeting Immune Checkpoints Potentiates Immunoediting and Changes the Dynamics of Tumor Evolution

Scientists elucidated the impact of evolutionary and immune-related forces on editing the tumor in a mouse model for hypermutated and microsatellite-instable colorectal cancer. Analyses of wild-type and immunodeficient RAG1 knockout mice transplanted with MC38 cells revealed that upregulation of checkpoint molecules and infiltration by Tregs are the major tumor escape mechanisms. [Nat Commun] Full Article

Optimizing Human Treg Immunotherapy by Treg Subset Selection and E-Selectin Ligand Expression

Researchers examined clinically-relevant activities of defined subsets of freshly-isolated and culture-expanded human PBMC-derived Tregs. Unlike highly suppressive but plastic memory Tregs, naïve Tregs exhibited the greatest proliferation, suppressive capacity after stimulation, and Treg lineage fidelity. [Sci Rep] Full Article

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

Updating Osteoimmunology: Regulation of Bone Cells by Innate and Adaptive Immunity

The active regulation of immune cells by bone cells is an interesting emerging component of investigations that seek to understand how to control immune-associated diseases of the bone and joints. [Nat Rev Rheumatol] Abstract

Regulatory T Cells as a New Therapeutic Target for Atherosclerosis

The authors present current knowledge of Treg subsets, summarize the relationship between Tregs and atherosclerosis development, and discuss the possibilities of regulating Tregs for prevention of atherosclerosis pathogenesis and enhancement of plaque stability. [Acta Pharmacol Sin] Abstract

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

Forty Seven Inc. to Collaborate with Merck KGaA, Darmstadt, Germany, on a Novel Immuno-Oncology Combination for Ovarian Cancer

Forty Seven Inc. announced an agreement with Merck KGaA, Darmstadt, Germany to conduct a Phase Ib clinical trial combining Hu5F9-G4 with avelumab in patients with ovarian cancer. [Forty Seven Inc.] Press Release

Syndax Pharmaceuticals Announces Clinical Collaboration to Evaluate Entinostat in Combination with Anti-PD-L1 Cancer Immunotherapy in Breast Cancer

Syndax Pharmaceuticals, Inc. announced a new clinical collaboration with Genentech. As part of the collaboration, the two companies will evaluate the combination of Syndax’s entinostat, an oral, small molecule, class I HDAC inhibitor, and Genentech’s programmed cell death ligand 1 (PD-L1) blocking antibody, atezolizumab, in patients with second-line hormone receptor positive, human epidermal growth factor receptor 2 negative metastatic breast cancer. [Syndax Pharmaceuticals, Inc.] Press Release

Rising Star Appointed UK Science Minister

The United Kingdom has gained a new science minister as part of a broader reshuffle of government posts. Sam Gyimah, who moves from the Ministry of Justice, was appointed minister for universities and science, replacing Jo Johnson. [Nature News] Editorial

Faced with Public Pressure, Research Institutions Step Up Reporting of Clinical Trial Results

The reporting of clinical trial results to a public database — mandated by a ten-year-old federal law — has improved sharply in the last two years, with universities and other nonprofit research centers leading the way. [STAT News] Editorial

NEW Cold Spring Harbor (CSH): Mechanisms & Models of Cancer
August 14-18, 2018
Cold Spring Harbor, New York, United States

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

NEW PhD Positions – Immunology (Regensburg Center for Interventional Immunology)

NEW Postdoctoral Fellow – Regulation of Platelet Mediated Complications (NYU School of Medicine)

NEW Postdoctoral Researcher – Human Microbiome-Immune System Interactions (University of Luxembourg)

Research Technologist – Cell Separation (STEMCELL Technologies Inc.)

Scientist – Immunology (STEMCELL Technologies Inc.)

Research Scientist – Cellular and Translational Immunology (University of Virginia)

Postdoctoral Fellow – Mechanisms of Immune Regulation (Rhode Island Hospital)

Postdoctoral Scholar – Immunology (Pennsylvania State University)

Postdoctoral Positions – Innate Immunity (University of Connecticut)

Postdoctoral Research Fellow – Inflammation and Immuno-Oncology (Yale School of Medicine)

Technical Research Assistant – Mucosal Immunology (Helmholtz Zentrum München)

Postdoctoral Training Opportunity – Infection and Immunity (Institut Pasteur of Shanghai – Chinese Academy of Sciences)

Postdoctoral Positions – RNA Regulation of T-Cell Based Cancer Immunology (The University of Texas MD Anderson Cancer Center)

Assistant, Associate, or Full Member – Cancer Immunology (Fred Hutchinson Cancer Research Center)

Research Fellow Position – Immunology Research (ShanghaiTech University)

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 Immune Regulation News? Click here to submit!

Comments or suggestions? Submit your feedback here.