Immune Regulation News Volume 11.39 | Oct 18 2019

TOP STORY

Mechanosensing by Peyer’s Patch Stroma Regulates Lymphocyte Migration and Mucosal Antibody Responses

Peyer’s patch fibroblastic reticular cells (FRCs) responded to conduit fluid flow via the mechanosensitive ion channel Piezo1. Disruption of fluid flow or genetic deficiency of Piezo1 on CCL19-expressing stroma led to profound structural alterations in perivascular FRCs and associated high endothelial venules. [Nat Immunol] Abstract

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Transcriptional Atlas of Intestinal Immune Cells Reveals that Neuropeptide α-CGRP Modulates Group 2 Innate Lymphoid Cell Responses

Computational analysis revealed broad shifts in both cell-type composition and cell programs in response to the inflammation, especially in group 2 innate lymphoid cells. [Immunity] Abstract | Graphical Abstract

T Cells Redirected against Igβ for the Immunotherapy of B Cell Lymphoma

The authors engineered T cells to express anti-Igβ CAR with CD28 costimulatory signaling moiety and observed that Igβ-CAR T cells could efficiently recognize and eliminate Igβ⁺ lymphoma cells both in vitro and in two different lymphoma xenograft models. [Leukemia] Abstract

Immune Cell PD-L1 Co-Localizes with Macrophages and Is Associated with Outcome in PD-1 Pathway Blockade Therapy

Researchers measured the expression of PD-L1 in multiple immune cells with two platforms and confocal microscopy on three retrospective Yale NSCLC cohorts. The PD-L1 level was selectively measured in different immune cell subsets using two multiplexed QIF panels including CD56 for natural killer cells, CD68 for macrophages and CD8 for cytotoxic T cells. [Clin Cancer Res] Abstract

Single-Cell Analysis Reveals Regulatory Gene Expression Dynamics Leading to Lineage Commitment in Early T Cell Development

Investigators established regulatory phenotypes of sequential early T cell precursor (ETP) subsets, confirmed initial co-expression of progenitor with T cell specification genes, defined stage-specific relationships between cell cycle and differentiation, and generated a pseudotime model from ETP to T lineage commitment, supported by RNA velocity and transcription factor perturbations. [Cell Syst] Abstract | Graphical Abstract

TET2 Regulates the Neuroinflammatory Response in Microglia

Scientists showed that Ten-eleven translocation 2 (TET2) methylcytosine dioxygenase expression was increased in microglia upon stimulation with various inflammogens through a NF-κB-dependent pathway. [Cell Rep] Full Article | Graphical Abstract

Breast Cancer Cells and PD-1/PD-L1 Blockade Upregulate the Expression of PD-1, CTLA-4, TIM-3 and LAG-3 Immune Checkpoints in CD4⁺ T Cells

Researchers found that breast cancer cells upregulate the expression of immune checkpoints including PD-1, cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) and lymphocyte activation gene-3 (LAG-3) in CD4⁺ T cell subsets. [Vaccines] Abstract | Download Full Article

Endoplasmic Reticulum Stress Differentially Modulates the IL-6 Family of Cytokines in Murine Astrocytes and Macrophages

The authors examined the expression of the interleukin (IL)-6 family cytokines in response to pharmacologically-induced endoplasmic reticulum (ER) stress in astrocytes and macrophages, which expressed IL-6 in response to ER stress through different mechanisms. [Sci Rep] Full Article

Dendritic Cells and Regulatory T Cells Expressing CCR4 Provide Resistance to Coxsackievirus B5-Induced Pancreatitis

Investigators found that coxsackievirus B5 infection induced CCL17 production and controlled the migration of CCR4⁺ DCs and CCR4⁺ Tregs to the pancreatic lymph nodes. [Sci Rep] Full Article

Shikonin Attenuates Hyperhomocysteinemia-Induced CD4⁺ T Cell Inflammatory Activation and Atherosclerosis in ApoE^−/− Mice by Metabolic Suppression

In splenic CD4⁺ T cells isolated from hyperhomocysteinemia (HHcy)-ApoE^−/− mice, shikonin treatment significantly inhibited HHcy-stimulated pyruvate kinase muscle isozyme 2 activity, interferon-γ secretion and the capacity of these T cells to promote macrophage proinflammatory polarization. [Acta Pharmacol Sin] Abstract

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Tissue-Resident Memory T Cells and Their Biological Characteristics in the Recurrence of Inflammatory Skin Disorders

The authors discuss recent insights into the generation, homing, retention, and survival of tissue resident memory T (T_RM) cells and share our perspectives on the biological characteristics of T_RM cells in the recurrence of inflammatory skin disorders. [Cell Mol Immunol] Abstract

Pathological Alteration and Therapeutic Implications of Sepsis-Induced Immune Cell Apoptosis

Scientists focus on describing the major apoptosis process of immune cells with respect to physiologic and molecular mechanisms. Further, advances in apoptosis-targeted treatment modalities for sepsis are also discussed. [Cell Death Dis] Full Article

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ImaginAb Signs Multi-Party Collaboration Agreement with Three Global Pharmaceutical Companies to Help Further Develop Company’s CD8 ImmunoPET Technology

ImaginAb, Inc. announced the signing of a multi-party collaboration agreement with AstraZeneca, Pfizer Inc. and Takeda Pharmaceutical Company Limited focused on furthering the clinical development of ImaginAb’s CD8 ImmunoPET technology. [ImaginAb, Inc.] Press Release

Incyte Announces that the REACH2 Pivotal Trial of Ruxolitinib (Jakafi^®) Meets Primary Endpoint in Patients with Steroid-Refractory Acute Graft-versus-Host Disease

Incyte Corporation announced positive results from the Novartis-sponsored pivotal Phase III REACH2 study evaluating ruxolitinib in patients with steroid-refractory acute graft-versus-host disease. [Incyte Corporation] Press Release

Aurinia Reports Last Patient Study Visit in Aurora Phase III Lupus Nephritis Study and Provides Update on ATM Facility

Aurinia Pharmaceuticals Inc. reported that the last patient study visit has occurred in the AURORA Phase III lupus nephritis study. [Aurinia Pharmaceuticals Inc.] Press Release

Principia Announces Positive Preliminary Data of PRN1008 for Immune Thrombocytopenia in Ongoing Phase I/II Trial

Principia Biopharma Inc. announced positive preliminary data from an ongoing Phase I/II trial of its investigational treatment, PRN1008, in a highly treatment-resistant and refractory patient population with immune thrombocytopenia. [Principia Biopharma Inc.] Press Release

Nektar Therapeutics Announces Initiation of First-in-Human Phase I Clinical Study of NKTR-255, an IL-15 Agonist, in Adults with Relapsed or Refractory Non-Hodgkin Lymphoma or Multiple Myeloma

Nektar Therapeutics announced the initiation of a first-in-human, Phase I clinical study evaluating NKTR-255, an interleukin-15 (IL-15) receptor agonist, as monotherapy for patients with relapsed or refractory non-Hodgkin lymphoma or multiple myeloma. [Nektar Therapeutics] Press Release

AbbVie Receives CHMP Positive Opinion for Upadacitinib (RINVOQ™) for the Treatment of Adults with Moderate to Severe Active Rheumatoid Arthritis

AbbVie announced that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion for RINVOQ™, a once-daily selective and reversible JAK inhibitor, for the treatment of adult patients with moderate to severe active rheumatoid arthritis who have responded inadequately to, or who are intolerant to one or more disease-modifying anti-rheumatic drugs. [AbbVie] Press Release

Merck Receives Positive EU CHMP Opinion for Two New Regimens of KEYTRUDA^® (Pembrolizumab) as First-Line Treatment for Metastatic or Unresectable Recurrent Head and Neck Squamous Cell Carcinoma

Merck announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has adopted a positive opinion recommending approval of two regimens of KEYTRUDA, Merck’s anti-PD-1 therapy, for the first-line treatment of metastatic or unresectable recurrent head and neck squamous cell carcinoma. [Merck & Co., Inc.] Press Release

I-Mab Biopharma and MorphoSys Announce IND Clearance to Initiate Clinical Trials of TJ202/MOR202 for the Treatment of Multiple Myeloma in Mainland China

I-Mab Biopharma and MorphoSys AG announced that I-Mab has received Investigational New Drug (IND) clearances from the National Medical Products Administration of China to expand the ongoing phase II and III clinical trials of TJ202/MOR202, MorphoSys’s human monoclonal anti-CD38 antibody for the treatment of multiple myeloma, also to mainland China. [I-Mab Biopharma] Press Release

Nplate^® (Romiplostim) Now Approved for Earlier Use in Adults with Immune Thrombocytopenia

Amgen announced that the FDA approved Amgen’s Supplemental Biologics License Application for Nplate^® to include new data in its US prescribing information showing sustained platelet responses in adults with immune thrombocytopenia, a rare, serious autoimmune disease characterized by low platelet counts. [Amgen] Press Release

Adaptate Biotherapeutics Formed to Develop Antibody-Based Therapies that Modulate Gamma Delta T-Cells

GammaDelta Therapeutics announced the formation of a spin-out company: Adaptate Biotherapeutics. While GammaDelta Therapeutics’ primary goal is to develop γδ T-cell based cell therapy products, the new spin-out will build on GammaDelta’s knowledge to modulate γδ T-cell activity using therapeutic antibodies, with the potential to trigger an immune response against cancer. [GammaDelta Therapeutics] Press Release

Brexit Hits UK Science Funding and Workforce

The first figures have emerged demonstrating that Brexit uncertainty has adversely affected UK research. They show Britain’s annual share of EU research funding has fallen by nearly a third since 2015. [The BBC] Editorial

Scientific Integrity Bill Advances in US House with Bipartisan Support

Despite their failure to attract a single Republican co-sponsor, Democrats in Congress have long insisted that a bill to strengthen scientific integrity across US government agencies takes a bipartisan stance and is not a veiled attack on the Trump administration’s attitude toward science. That claim of bipartisanship took a big step forward as the science committee of the US House of Representatives tweaked the bill to satisfy key Republicans on the panel. [ScienceInsider] Editorial

NEW 12^th European Lupus Meeting
March 25-27, 2020
Bruges, Belgium

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NEW Postdoctoral Research Fellow – Neuro-Immune Control of Metabolism (Fred Hutchinson Cancer Research Center)

Scientist – Human Immunology (STEMCELL Technologies Inc.)

Postdoctoral Position – Translational Immuno-Oncology (Institute for Tumor Biology and Experimental Therapy)

Postdoctoral Fellow – Immunology and Vaccines (University of Maryland)

Postdoctoral Research Associate – Innate Immune Signaling Pathways and Mechanisms (University of Utah)

Chief – Laboratory of Allergic Diseases (National Institute of Allergy and Infectious Diseases)

Postdoctoral Fellow – Cancer Immunology (University of Alabama at Birmingham)

Postdoctoral Position – Interface of Stem Cell Biology and Immunology (Columbia University)

Faculty Position – Tumor Immunology (University of Utah)

Assistant Professor and Postdoctoral Fellows – Immunology (Chinese Academy of Sciences)

Assistant Professor – Neuro-Immune/Neuro-Pharmacological Interactions (University of Pennsylvania)

Associate or Full Professor – Neuro-Immune/Neuro-Pharmacological Interactions (University of Pennsylvania)

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