Immune Regulation News Volume 11.21 | Jun 14 2019

TOP STORY

Cooperation between Constitutive and Inducible Chemokines Enables T Cell Engraftment and Immune Attack in Solid Tumors

Researchers investigated the role of chemokines in regulating T cell accumulation in solid tumors. CCL5 and CXCL9 overexpression was associated with CD8⁺ T cell infiltration in solid tumors. [Cancer Cell] Abstract | Press Release | Graphical Abstract

(Ranked by impact factor of the journal)

Targeting Tumors with IL-10 Prevents Dendritic Cell-Mediated CD8⁺ T Cell Apoptosis

Scientists generated Cetuximab-based IL-10 fusion protein (CmAb-(IL10)₂) to prolong its half-life and allow tumor-targeted delivery of IL-10. They demonstrated potent antitumor effects of CmAb-(IL10)₂ with reduced toxicity. [Cancer Cell] Abstract | Graphical Abstract

The Deubiquitinase Otub1 Controls the Activation of CD8⁺ T Cells and NK Cells by Regulating IL-15-Mediated Priming

The authors showed that IL-15 mediated homeostatic priming of CD8⁺ T cells for antigen-stimulated activation, which was controlled by a deubiquitinase, Otub1. IL-15 mediated membrane recruitment of Otub1, which inhibited ubiquitin-dependent activation of AKT, a kinase that is pivotal for T cell activation and metabolism. [Nat Immunol] Abstract

Tumor-Targeted 4-1BB Agonists for Combination with T Cell Bispecific Antibodies as Off-the-Shelf Therapy

The combination of FAP^– or CD19^–4-1BBL with CEA-TCB or CD20-TCB, respectively, resulted in tumor remission in mouse models, accompanied by intratumoral accumulation of activated effector CD8⁺ T cells. [Sci Transl Med] Full Article

LIF Regulates CXCL9 in Tumor-Associated Macrophages and Prevents CD8⁺ T Cell Tumor-Infiltration Impairing Anti-PD1 Therapy

Investigators observed that the blockade of LIF in tumors expressing high levels of LIF decreased CD206, CD163 and CCL2 and induced CXCL9 expression in tumor-associated macrophages. The blockade of LIF releases the epigenetic silencing of CXCL9 triggering CD8⁺ T cell tumor infiltration. [Nat Commun] Full Article

Autophagy Metabolically Suppresses CD8⁺ T Cell Antitumor Immunity

Scientists showed that deletion of the essential autophagy genes Atg5, Atg14, or Atg16l1 in host tissues dramatically impaired growth of autophagy-competent syngeneic tumors. [Autophagy] Abstract

KDM2B Promotes IL-6 Production and Inflammatory Responses through Brg1-Mediated Chromatin Remodeling

Researchers report that lysine-specific demethylase 2b (KDM2B), which demethylates H3K4me3 and H3K36me2, was required in macrophages and dendritic cells for the induction of IL-6 but not TNF-α, IL-1, and IFN-β. [Cell Mol Immunol] Abstract

miR-21 Promotes NLRP3 Inflammasome Activation to Mediate Pyroptosis and Endotoxic Shock

The authors showed that miR-21 deficiency inhibited NLRP3, ASC, and caspase-1 expression, as well as inflammasome activation in myeloid cells from both mice and humans. [Cell Death Dis] Full Article

Infiltrating CCR2⁺ Monocytes and Their Progenies, Fibrocytes, Contribute to Colon Fibrosis by Inhibiting Collagen Degradation through the Production of TIMP-1

During chronic inflammation, CC chemokine receptor 2 (CCR2)⁺ bone marrow (BM)-derived monocyte and fibrocyte infiltration into the colon and CC chemokine ligand 2 production increased, leading to colon fibrosis in enhanced green fluorescent protein BM chimeras. [Sci Rep] Full Article

Interleukin-17 Receptor D Constitutes an Alternative Receptor for Interleukin-17A Important in Psoriasis-Like Skin Inflammation

In a psoriasis model, researchers found that Il17rc deficiency did not completely ameliorate the disease, suggesting another receptor. [Sci Immunol] Full Article

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Interferon-λ Orchestrates Innate and Adaptive Mucosal Immune Responses

The authors highlight recent work showing that interferon-λ inhibits virus dissemination within the body and limits the transmission of respiratory and gastrointestinal viruses to naive hosts. [Nat Rev Immunol] Abstract

The Potential of Astrocytes as Immune Modulators in Brain Tumors

Scientists discuss the link between reactive astrocytes and the neuro-immune axis with a perspective on their potential importance in brain tumors. [Front Immunol] Full Article

Regulation of Innate Immune Responses by Platelets

Researchers present pointers to a better understanding about how platelets control and modulate innate immune cells, as well as a summary of the outcome of this interaction, providing an important step for therapeutic opportunities and guidance for future research on infectious and autoimmune diseases. [Front Immunol] Full Article

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

New Long-Term Data from Upadacitinib Phase III Studies in Rheumatoid Arthritis including Results on Clinical Remission at 48 Weeks Presented

AbbVie announced new results from the Phase III clinical trials SELECT-EARLY and SELECT-COMPARE showing that patients receiving upadacitinib once-daily through 48 weeks continue to demonstrate improved signs and symptoms of rheumatoid arthritis, as measured by ACR20/50, and clinical remission based on Disease Activity Score 28 C-Reactive Protein <2.6. [Press release from AbbVie (PR Newswire Association LLC.) discussing research to be presented at the European League Against Rheumatism (EULAR) 2019 Annual Meeting, Madrid] Press Release

Resolve Therapeutics Announces RSLV‐132 Significantly Reduces Fatigue in Phase II Study of Patients with Sjögren’s Syndrome

Resolve Therapeutics announced positive results from the Phase II study of RSLV‐132, an investigational treatment for primary Sjögren’s syndrome. [Press release from Resolve Therapeutics discussing research presented at the European League Against Rheumatism (EULAR) 2019 Annual Meeting, Madrid] Press Release

Kezar Life Sciences Announces Promising Data from First in Patient Study of KZR-616

Kezar Life Sciences, Inc. announced positive results from the Phase Ib open-label dose escalation portion of the MISSION study evaluating KZR-616 in patients with systemic lupus erythematosus. [Press release from Kezar Life Sciences, Inc. discussing research to be presented at the European League Against Rheumatism (EULAR) 2019 Annual Meeting, Madrid] Press Release

First-in-Human Data Presented from Phase Ia Study of NKTR-358, a Novel T Regulatory Cell Stimulator

Nektar Therapeutics announced the results of the first-in-human Phase Ia study evaluating single-ascending doses of NKTR-358, a first-in-class T regulatory cell stimulator in clinical development for the treatment of autoimmune and other chronic inflammatory conditions. [Press release from Nektar Therapeutics discussing research presented at the European League Against Rheumatism (EULAR) 2019 Annual Meeting, Madrid] Press Release

Merck to Acquire Tilos Therapeutics

Merck announced that it has entered into a definitive agreement to acquire Tilos Therapeutics, a privately held biopharmaceutical company developing therapeutics targeting the latent TGFβ complex for the treatment of cancer, fibrosis and autoimmune diseases. [Merck & Co., Inc.] Press Release

Kiadis Pharma Completes Acquisition of Cytosen Therapeutics, Inc.

Kiadis Pharma N.V. announces that it has closed the previously announced acquisition of CytoSen Therapeutics, Inc. [Kiadis Pharma N.V.] Press Release

Big Changes Needed to Fight Harassment, Group Tells US Biomedical Agency

The US National Institutes of Health (NIH) should make sweeping changes to how it funds research as part of its efforts to reduce sexual harassment in science, a working group advising the agency on the issue said on 13 June. The NIH should treat sexual misconduct as seriously as research misconduct, the group told agency director Francis Collins and his top advisers at a meeting in Bethesda, Maryland. [Nature News] Editorial

Wellcome Sanger Institute to Close Animal Facility

The Wellcome Sanger Institute announced that it would be closing its animal facility, which provides mice, zebrafish, rats, and frogs to geneticists at the institute and internationally, reports Nature. The institute states that the closure is related to the growing use of cell lines and organoids, instead of animals. [The Scientist] Editorial

NEW 19^th International Congress of Mucosal Immunology (ICMI)
July 19-20, 2019
Brisbane, Australia

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

NEW 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)

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

Postdoctoral Fellow – Cancer Checkpoint Immunotherapy (City of Hope)

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

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