Immune Regulation News Volume 11.22 | Jun 21 2019

TOP STORY

TOX Transcriptionally and Epigenetically Programs CD8⁺ T Cell Exhaustion

Researchers identified the HMG-box transcription factor TOX as a central regulator of exhausted CD8⁺ T cells (T_EX). TOX was largely dispensable for effector CD8⁺ T cell and memory CD8⁺ T cell formation, but was critical for exhaustion and without TOX T_EX do not form. [Nature] Abstract | Press Release

(Ranked by impact factor of the journal)

Distinct Modes of Mitochondrial Metabolism Uncouple T Cell Differentiation and Function

Scientists demonstrated that distinct modes of mitochondrial metabolism support differentiation and effector functions of mouse T helper 1 cells by biochemically uncoupling these two processes. [Nature] Abstract

Akkermansia muciniphila Induces Intestinal Adaptive Immune Responses during Homeostasis

The authors showed that A. muciniphila, an intestinal bacterium associated with systemic effects on host metabolism and PD-1 checkpoint immunotherapy, induces immunoglobulin G1 antibodies and antigen-specific T cell responses in mice. [Science] Abstract

A Temporal Thymic Selection Switch and Ligand Binding Kinetics Constrain Neonatal Foxp3⁺ T_reg Cell Development

Investigators identified 17 self-peptides recognized by neonatal thymus generated Foxp3⁺ regulatory T cells, and revealed ligand specificity patterns that included self-antigens presented in an age- and inflammation-dependent manner. [Nat Immunol] Abstract

Single-Cell RNA-Seq Reveals TOX as a Key Regulator of CD8⁺ T Cell Persistence in Chronic Infection

By comparing the single-cell transcriptomes and epigenetic profiles of CD8⁺ T cells responding to acute and chronic viral infections, researchers found that progenitor-like CD8⁺ T cells became distinct from memory precursor cells before the peak of the T cell response. [Nat Immunol] Abstract

Single-Cell RNA Sequencing of the T Helper Cell Response to House Dust Mites Defines a Distinct Gene Expression Signature in Airway Th2 Cells

Investigators performed single-cell RNA sequencing (scRNA-seq) of T helper (Th) cells from lymph node, lung, and airways in the house dust mite model of allergic airway disease. scRNA-seq resolved transcriptional profiles of naive CD4⁺ T, Th1, Th2, regulatory T cells, and a CD4⁺ T cell population responsive to type I interferons. [Immunity] Abstract | Graphical Abstract

The Intestine Harbors Functionally Distinct Homeostatic Tissue-Resident and Inflammatory Th17 Cells

Scientists compared the characteristics of T helper 17 (Th17) cells differentiating in response to commensal bacteria to those differentiating in response to a pathogen. Homeostatic Th17 cells exhibited little plasticity towards expression of inflammatory cytokines, were characterized by a metabolism typical of quiescent or memory T cells, and did not participate in inflammatory processes. [Immunity] Abstract | Graphical Abstract

A Mucin 16 Bispecific T Cell-Engaging Antibody for the Treatment of Ovarian Cancer

The authors describe a human bispecific antibody that binds both Mucin 16 (MUC16), a glycoprotein that is highly expressed on ovarian cancer cells, and CD3, thus bridging MUC16-expressing cells with CD3⁺ T cells. [Sci Transl Med] Abstract

IL-33-Mediated Mast Cell Activation Promotes Gastric Cancer through Macrophage Mobilization

Investigators found that genetic ablation or therapeutic inactivation of mast cells suppressed accumulation of tumor-associated macrophages, reduced tumor cell proliferation and angiogenesis, and diminished tumor burden. [Nat Commun] Full Article

Fcmr Regulates Mononuclear Phagocyte Control of Anti-Tumor Immunity

Scientists demonstrated that Fcmr, the putative receptor for soluble IgM, modulated myeloid cell responses to cancer. In a syngeneic melanoma model, Fcmr ablation in myeloid cells suppressed tumor growth and extended mouse survival. [Nat Commun] Full Article

Cathepsin G Inhibition by Serpinb1 and Serpinb6 Prevents Programmed Necrosis in Neutrophils and Monocytes and Reduces GSDMD-Driven Inflammation

Researchers showed that the intracellular protease inhibitors Serpinb1a and Serpinb6a contribute to monocyte and neutrophil survival in steady-state and inflammatory settings by inhibiting cathepsin G. [Cell Rep] Full Article | Graphical Abstract

Intratumoral Activation of the Necroptotic Pathway Components RIPK1 and RIPK3 Potentiates Antitumor Immunity

The authors showed that ectopic introduction of necroptotic cells to the tumor microenvironment promotes BATF3⁺ cDC1⁻ and CD8⁺ leukocyte-dependent antitumor immunity accompanied by increased tumor antigen loading by tumor-associated antigen-presenting cells. [Sci Immunol] Full Article

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γδ T Cells: Pleiotropic Immune Effectors with Therapeutic Potential in Cancer

Researchers outline both seminal work and recent advances in the understanding of how γδ T cells participate in tumor immunity and how their functions are regulated in experimental models of cancer. [Nat Rev Cancer] Abstract

Adaptation and Memory in Immune Responses

Scientists review and analyze mechanisms of adaptation and memory in immunity with the aim of providing basic concepts that rationalize the properties and molecular bases of these essential processes. [Nat Immunol] Abstract

Metabolic Adaptations of Tissue-Resident Immune Cells

The authors discuss the available data on the metabolic adaptation of immune cells to life in different tissue sites, within the broader framework of how functional adaptation versus maladaptation in the niche can affect tissue homeostasis. [Nat Immunol] Abstract

Systemic Effects of IL-17 in Inflammatory Arthritis

After a brief description of IL-17 and its local effects on joints, investigators focus on the systemic effects of IL-17 in inflammatory arthritis. [Nat Rev Rheumatol] Abstract

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

Gilead and Nurix Establish Strategic Collaboration to Develop Novel Therapies for Cancer and Other Diseases

Gilead Sciences, Inc. and Nurix Therapeutics, Inc. announced a global strategic collaboration to discover, develop and commercialize a pipeline of innovative targeted protein degradation drugs for patients with cancer and other challenging diseases. [Gilead Sciences, Inc.] Press Release

SOFIE and University Clinic Heidelberg Sign License Agreement

SOFIE Inc. announced an exclusive global license with University Clinic Heidelberg for a class of molecular targeted diagnostics and radiotherapeutics that are designed to identify and break down cancer associated fibroblasts in tumor stroma and irradiate nearby cancer cells. [SOFIE Inc.] Press Release

Pfizer to Acquire Array Biopharma

Pfizer Inc. and Array BioPharma Inc. announced that they have entered into a definitive merger agreement under which Pfizer will acquire Array, a commercial stage biopharmaceutical company focused on the discovery, development and commercialization of targeted small molecule medicines to treat cancer and other diseases of high unmet need. [Pfizer Inc.] Press Release

Boehringer Ingelheim and OSE Immunotherapeutics Announce Dosing of the First Patient in a Phase I Trial of SIRPα Antagonist Monoclonal Antibody, BI 765063, in Patients with Advanced Solid Tumors

Boehringer Ingelheim and OSE Immunotherapeutics SA announced that the first patient has been dosed in the first-in-human Phase I clinical trial evaluating BI 765063, formerly OSE-172, a first-in-class monoclonal antibody antagonist of SIRPα, being studied in patients with advanced solid tumors. [Boehringer Ingelheim International GmbH] Press Release

Alligator Bioscience Submits Clinical Trial Application for ATOR-1017

Alligator Bioscience announced that the company has submitted clinical trial authorization application to initiate a Phase I study of its fully owned 4-1BB antibody ATOR-1017 for the treatment of metastasizing cancer. [Alligator Bioscience AB] Press Release

New NIH Funding Will Support Research into How the Body Responds to Medical Implants

A Virginia Commonwealth University engineering professor has received a $1.76 million grant to further his research on tissue healing and investigate how immune system cells control the body’s response to biomaterials such as a dental implant or hip replacement. [Virginia Commonwealth University] Press Release

Mill Creek Life Sciences Receives Grant from Regenerative Medicine Minnesota for Development of Dendritic Cell Vaccine

Mill Creek Life Sciences, LLC has received a one-year $100,000 grant from Regenerative Medicine Minnesota titled: “Development of Technology for the Large-scale Production of a Novel Dendritic Cell Vaccine for the Treatment of Glioblastoma.” [Mill Creek Life Sciences, LLC (PR Newswire Association LLC.)] Press Release

House Panel Clarifies How Universities Would Report Sexual Harassment Cases to US Funders

New rules from the National Science Foundation (NSF) on reporting sexual harassment by someone with an NSF grant raise questions about due process, university administrators say. A key congressional panel took those concerns to heart by modifying language in a bill that would require the administration to write guidelines applying to half a dozen major federal research agencies. [ScienceInsider] Editorial

Academics Join Outcry Sparked by Hong Kong’s Contentious Extradition Bill

Since the bill that would legalize the extradition of people from Hong Kong to mainland China to stand trial or serve criminal sentences was announced, more than a thousand academics from around the world have signed a petition against the proposed law, saying it would restrict free speech and academic debate as well as eroding personal freedoms. [Nature News] Editorial

NEW 14^th World Congress on Inflammation Sydney 2019
September 15-19, 2019
Sydney, Australia

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

NEW PhD Scholarships – Systems Biology in Immune and Infectious Diseases (University of Perugia)

Postdoctoral Position – Immunology (KU Leuven)

Postdoctoral Position – Genetics & Immunology (Columbia University Medical Center)

Postdoctoral Position – Cancer Immunology (Feinberg School of Medicine-Northwestern University)

Researcher – Tumor Responses to Radiotherapy & Immunotherapy (University Hospital of Northern Norway)

Postdoctoral Fellow – Innate Immunity & Inflammation (University of Pennsylvania)

Postdoctoral Fellow – Intracellular Innate Immunity (EPFL)

Postdoctoral Fellow – Transplantation Immunology (Medical College of Wisconsin)

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

Postdoctoral Fellow – Cancer Checkpoint Immunotherapy (City of Hope)

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

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